INTRODUCTION TO STRUCTURAL VIROLOGY PART ONE: FOUNDATIONS
BY RON SHEVUAH
[email protected] A ONE-HOUR EXPOSITION WITH COMPLETE TECHNICAL REFERENCES 1-7-2010
STANDARD COPYRIGHT BLAH-BLAH BOILERPLATE THE MATERIAL CONTAINED IN THIS WORK IS COPYRIGHT © 2011, BY RON SHEVUAH. ALL RIGHTS RESERVED. THIS MATERIAL MAY BE USED FOR ANY NON-PROFIT PURPOSE, NO PERMISSION REQUIRED. BOOK AUTHORS, OR ANY OTHER FOR-PROFIT PURPOSE, MAY CONTACT ME FOR ARRANGEMENTS. ALL USAGE OF THE MATERIAL CONTAINED HEREIN MUST BE ACKNOWLEDGED AS THE WORK OF RON SHEVUAH.
COPYRIGHT HAIKU: USE THIS FOR TEACHING BUT IF YOU MAKE SOME MONEY THEN WE GOTTA TALK I THINK THAT SUMS IT UP PRETTY GOOD.
PART I: WHAT IS A VIRUS?
THIS IS NOT A VIRUS. THIS IS THE FIGMENT OF A REALLY BAD FILMMAKER’S IMAGINATION.
VIRUSES DON’T HAVE TEETH.
WHAT ARE VIRUSES? THEY ARE THE SMALLEST, SIMPLEST POSSIBLE LIFEFORM.
BAKER 1988, FIG. 3
MOST OF THEM CONSIST OF JUST THEIR NUCLEIC ACID GENOMES, WRAPPED IN A COATING OF PROTEIN.
NUCLEIC ACID IS A STRING OF BASES. IT TAKES THE FORM OF EITHER DNA or RNA. THEY BOTH HAVE 4 DIFFERENT BASES. AS YOU CAN SEE, DNA AND RNA ARE EXTREMELY SIMILAR.
ALL THE CELLULAR LIFE-FORMS ON EARTH USE DNA FOR THEIR GENETIC STORAGE MEDIUM, THAT IS, THEIR GENOME. THIS IS DOUBLE-STRANDED DNA.
DOUBLE-STRANDED DNA CONSISTS OF 2 SEPARATE STRANDS RUNNING IN OPPOSITE DIRECTIONS, AND BONDED TOGETHER AT THE BASES. THE STRANDS ARE THEN TWISTED INTO THE FAMILIAR DOUBLE HELIX.
THYMINE
CYTOSINE
GUANINE
ADENINE
VIRUSES ARE DIFFERENT. DIFFERENT VIRAL SPECIES HAVE ALL FOUR OF THE MAJOR TYPES OF NUCLEIC ACID: DOUBLE-STRAND DNA (dsDNA), SINGLE-STRAND DNA (ssDNA), DOUBLESTRAND RNA (dsRNA), AND SINGLE-STRAND RNA (ssRNA):
dsDNA
ssDNA
dsRNA
ssRNA
THESE ARE SOME OF THE BEST KNOWN VIRAL GROUPS, AND THE TYPE OF NUCLEIC ACID THAT MAKES UP THEIR GENOME. VIRAL FAMILES HAVE THE SUFFIX “VIRIDAE”.
dsDNA ADENOVIRIDAE HEPADNAVIRIDAE (HEPATITIS) HERPESVIRIDAE (EPSTEIN BARR, HERPES SIMPLEX) PAPILLOMAVIRIDAE POXVIRIDAE
dsRNA BIRNAVIRIDAE (INFECTIOUS BURSAL DISEASE VIRUS) REOVIRIDAE (REOVIRUS, ROTAVIRUS)
ssDNA CIRCOVIRIDAE MICROVIRIDAE PARVOVIRIDAE (CANINE PARVOVIRUS)
ssRNA CALICIVIRIDAE (NORWALK) CORONAVIRIDAE (SARS) PICORNAVIRIDAE (POLIO, RHINOVIRUS) RETROVIRIDAE (HIV) RHABDOVIRIDAE (RABIES) TOGAVIRIDAE
DNA
PROTEIN
G C
TRANSCRIPTION & TRANSLATION
R
(ARGININE)
TRANSCRIPTION & TRANSLATION
G
(GLYCINE)
D
(ASPARTIC ACID)
A C C
A C T G
TRANSCRIPTION & TRANSLATION
3 BASES, BY THE PROCESSES OF TRANSCRIPTION AND TRANSLATION, ARE COPIED AS A SINGLE AMINO ACID. PROTEIN IS A STRING OF AMINO ACIDS. THERE ARE 20 DIFFERENT ONES.
THE 20 AMINO ACIDS:
THE 20 AMINO ACIDS: (CONTINUED)
THESE AMINO ACIDS FORM LONG STRINGS. A TYPICAL PROTEIN HAS BETWEEN 200 AND 400 OF THEM.
R
K N D
E Q
H
P
Y
S T W
G
A M C
F
L
V
I
ONCE FORMED, THE STRING SNAPS INTO A DISTINCTIVE SHAPE: A PROTEIN SUBUNIT. THE FUNCTIONALITY OF PROTEIN DEPENDS ON THE PERFECT CONSISTENCY OF THAT SHAPE.
HYDROPATHY IS A NUMERICAL GUAGE OF HOW WELL AN AMINO ACID MIXES WITH WATER. THE ONES THAT ARE ATTRACTED TO WATER ARE ON THE LEFT SIDE; THE ONES REPELLED BY WATER ARE ON THE RIGHT.
Q E D K H R N
MORE HYDROPHILIC (WATER-LOVING)
G S Y T P W
M A C
see LEHNINGER et al, “PRINCIPLES OF BIOCHEMISTRY”, VARIOUS EDITIONS.
I F
V L
MORE HYDROPHOBIC (WATER-HATING)
THE DISTINCTIVE FOLDING OF A PROTEIN IS PRIMARILY DETERMINED BY THE HYDROPATHY OF ITS AMINO ACIDS: THE HYDROPHOBIC ONES TRY TO BURY THEMSELVES ON THE INSIDE.
THE HYDROPHILIC ONES LIKE TO BE ON THE OUTSIDE, WHERE THEY MIX WITH THE WATERY ENVIRONMENT IN WHICH PROTEINS FORM: THE INTERIORS OF CELLS.
HYDROPHILES
E
D HYDROPHOBES
Q K
L V I A C M F
H
N R
UPON FORMATION, A PROTEIN SUBUNIT WILL HAVE BOTH POSITIVE AND NEGATIVE CHARGES ON THE OUTSIDE. A FEW OF THE AMINO ACIDS ARE POSITIVE AND A FEW ARE NEGATIVE; THESE ARE THE MOST LIKELY TO BE PUSHED TO THE OUTSIDE DURING THE PROCESS OF PROTEIN FOLDING. THESE POSITIVE AND NEGATIVE CHARGES ARE COLLECTIVELY KNOWN AS ELECTROSTATIC FORCES.
THE MAJORITY OF VIRUSES ASSEMBLE THEMSELVES WITHOUT ANY HELP. THE PROTEIN SUBUNITS COME TOGETHER, FITTING THEMSELVES LIKE AN ELECTROSTATIC (3D) JIGSAW PUZZLE. THEY FLY TOGETHER AS IF THEY WERE LITTLE MAGNETS—LIKE CHARGES REPEL, AND UNLIKE CHARGES ATTRACT.
VIRUSES ARE SOMETIMES REFERRED TO AS MACROMOLECULAR COMPLEXES…IN OTHER WORDS, CLUSTERS OF MOLECULES.
THE FORMATION OF A VIRUS INVOLVES NO GROWTH, IN THE TRUE METABOLIC SENSE.
VIRAL FORMATION IS MORE LIKE A NUCLEATION PROCESS…THE SHELL IS ESSENTIALLY A PROTEIN CRYSTAL, AS IT WERE. THIS ALONE MAKES THEM STRIKINGLY DIFFERENT FROM OTHER LIFE-FORMS.
MORE SOPHISTICATED VIRUSES ARE FORMED IN SOMETHING LIKE AN ASSEMBLY LINE PROCESS. LIKE ALL VIRUSES, THEY ARE FORMED FROM PREFABRICATED COMPONENTS. AND LIKE ALL VIRUSES, THEY HAVE AN EXTREMELY CONSISTENT STRUCTURE.
see PORANEN 2004, FIG. 2
HOW
CONSISTENT?
THIS IS SATELLITE TOBACCO MOSAIC VIRUS (STMV). IT’S ONE OF THE MOST SIMPLE VIRUSES. IT HAS EXACTLY 1,066,628 ATOMS IN ITS’ STRUCTURE (FREDDOLINO 2006). IT ISN’T POSSIBLE TO COUNT THE ATOMS OF ANY OTHER TYPE OF ORGANISM.
1,066,628 ATOMS
VIRUSES ARE UNLIKE ANY OTHER TYPE OF LIFE-FORM. EVERY ATOM IS ACCOUNTED FOR, AND DIRECTLY SPECIFIED BY ITS GENETIC CODE.
CELLULAR LIFE-FORMS HAVE VARIATIONS BETWEEN INDIVIDUALS OF THE SAME SPECIES.
VIRUSES ARE CARBON COPIES OF EACH OTHER. A VIRUS IS A MATHEMATICAL FORMULA, ETCHED IN PROTEIN.
=
=
=
A VIRUS DOES NOT EAT, DRINK, OR BREATHE. IT DOESN’T EXPERIENCE THE NEEDS OF LIVING THINGS.
“I HATE VIRUSES…THEY JUST SIT THERE ALL DAY, AND NEVER ORDER ANYTHING!”
PARTIES THROWN BY VIRUSES TEND TO BE EXTREMELY DULL…EVEN BACTERIA SAY SO.
“NO CAKE, NO BEER, NO AIR—THIS IS THE WORST PARTY IV’E EVER BEEN TO!”
IN CONTRAST, BACTERIA ACTUALLY EAT THINGS, AND CHANGE THEM INTO OTHER THINGS…THIS IS PROOF OF METABOLISM.
WHEN FOOD SPOILS, THIS IS BECAUSE OF BACTERIAL METABOLISM: CHEMICAL CHANGES IN THE FOOD, CAUSED BY BACTERIAL DIGESTION AND ELIMINATION. BACTERIA ARE NATURAL CHEMISTS.
A CELL IS AN ENCLOSED BAG OF FLUID WHERE MANY COMPLEX CHEMICAL REACTIONS TAKE PLACE SIMULTANEOUSLY.
THESE CHEMICAL REACTIONS ARE COLLECTIVELY REFERRED TO AS METABOLISM. METABOLISM IS A TRADITIONAL MEASURE OF LIFE ITSELF.
VIRUSES HAVE NO LIQUID INTERIOR, SO THEY ARE METABOLICALLY INERT MOST OF THE TIME.
VIRUS
CELL
VIRUSES HAVE ESSENTIALLY NO METABOLISM AT ALL. SOME UTILIZE ATP—THE FUEL OF CELLS—WHILE PACKAGING THEIR GENOME. THIS IS ABOUT AS CLOSE TO METABOLISM AS THEY GET.
THIS ONE HAS TO SPEND CHEMICAL ENERGY, TO PACK THE DNA INSIDE ITS HEAD.
NOTICE THAT THE METABOLISM, AS SUCH, OCCURS OUTSIDE OF ITS “BODY”.
CAPSID
ADP + Pi DNA PACKAGING PROTEINS
ATP
DIRECTION OF DNA TRANSPORT AND PACKAGING see LEE 2006D, FIG. 7
ARE VIRUSES A SIXTH KINGDOM OF LIFE? THE FIVE KINGDOM SCHEME HAS BEEN THE MAIN DOGMA IN BIOLOGY FOR DECADES
CELLULAR LIFE-FORMS 1. ANIMALS
2. PLANTS (FLOWERING, PHOTOSYNTHETIC)
3. FUNGI NON-FLOWERING, NONPHOTOSYNTHETIC PLANTS
4. PROTOZOANS—ONE-CELLED CREATURES WITH A NUCLEUS
5. BACTERIA—ONE-CELLED CREATURES WITHOUT A NUCLEUS
NON-CELLULAR LIFE-FORMS 6. VIRUSES…?
7. VIROIDS, PRIONS…? (SUB-CAPSIDAL LIFE-FORMS)
ARE VIRUSES ACTUALLY ALIVE? BIOLOGISTS ARE DIVIDED. IT’S
ALIVE!!!
YOU’RE A
LOONIE!
WELL, AT LEAST IT’S GENERALLY AGREED THAT BIOLOGISTS ARE ALIVE.
A VIRUS HAS ABOUT THE SAME KIND OF LIFE AS A PLANT SEED:
VIRUS
OUTSIDE OF ITS FUNCTIONING ENVIRONMENT, IT SHOWS NO SIGNS OF LIFE.
CELLS
INSIDE OF ITS FUNCTIONING ENVIRONMENT, IT BEGINS TO ACT LIKE A LIVING THING.
THEY CANNOT MULTIPLY IN DEAD CELLS. THEY REQUIRE THE FUNCTIONING MECHANISMS IN LIVING CELLS IN ORDER TO REPRODUCE: THEY DON’T HAVE ENOUGH GENES TO DO THAT BY THEMSELVES. EWW, ICKY!
TOTALLY GROSS!
A VIRUS IS AN INERT PARTICLE, UNTIL IT GAINS ENTRY INTO A LIVING CELL. IT DEPENDS ON THE LIFE FORCE OF THE CELL TO GIVE IT THE SEMBLANCE OF LIFE.
THE VIRUS RELEASES ITS GENOME INTO THE INTERIOR OF THE CELL, THEN TAKES OVER THE GENETIC MACHINERY TO MAKE COPIES OF ITSELF.
WHEN A VIRUS PENETRATES A CELL, IT UNCOATS, AND THEN PIRATES THE NUCLEUS. THIS IS THE ONLY TIME IT APPEARS TO BE ALIVE. WITHOUT THE PRESENCE OF CELLULAR LIFE FORMS, VIRUSES HAVE NO LIFE SIGNS AT ALL. THEY ARE RELEASED FROM A CELL IN CONSIDERABLE NUMBERS; THIS NUMBER IS CALLED THE BURST SIZE. BURST SIZE VARIES FROM TENS TO HUNDREDS OF VIRIONS PER CELL, DEPENDING ON THE VIRAL SPECIES (WOMMACK 2000). See BAKER 1999, FIG. 15
PART II: VIRUSES ARE SMALL So, naturalists observe, a flea Hath smaller fleas that on him prey; And these have smaller still to bite 'em, And so proceed ad infinitum. Jonathan Swift
VIRUSES ARE SUB-MICROSCOPIC. AN INDIVIDUAL PLANT/ANIMAL CELL (LEFT) IS HUGE BY COMPARISON. EVEN BACTERIA (CENTER), THE SMALLEST TYPE OF CELLULAR LIFE-FORM, IS MUCH BIGGER.
CELL (~20 MICRONS)
A VIRUS (FAR RIGHT) IS THE SMALLEST LIVING THING. THE TINY DOT SHOWN HERE WOULD ACTUALLY BE A LARGE ONE.
E. COLI (1 x 4 MICRONS)
VIRUS (GENERALLY UNDER 100 NANOMETERS)
HERE ARE SOME OF THE VIRAL TYPES, COMPARED TO E. COLI. E. COLI IS ABOUT 1 MICRON (1,000 NM) BY 4 MICRONS (4,000 NM).
4µ
1µ (ALL TO SCALE)
THIS IS A CLOSER VIEW, SHOWING MIMIVIRUS (THE LARGEST CIRCLE), 500 NM; HERPES, 125 NM; REOVIRUS, 85 NM; PAPILLOMAVIRUS, 60 NM; RHINOVIRUS, 32 NM; SPMV, 16 NM. THE LONG TUBE IS TOBACCO MOSAIC VIRUS, 18 x 300 NM; THE TROMBONE IS M-13, 7 x 600 NM; THE STRANGE BUG SHAPE IS T-4, 180 NM IN HEIGHT.
VIRUSES ARE SMALLER THAN THE WAVELENGTH OF LIGHT, SO THEY’RE TOO SMALL TO REFLECT IT.
BLUE LIGHT
RED LIGHT
THIS IS WHY THEY DON’T APPEAR UNDER A LIGHT MICROSCOPE.
VIRUSES CAN ONLY BE SEEN WITH AN ELECTRON MICROSCOPE. ELECTRONS HAVE A SMALLER WAVELENGTH THAN VISIBLE LIGHT.
ANY CELLULAR LIFEFORM CAN CATCH A VIRUS
see KELLER 1988
THIS E. COLI IS UNDER ATTACK BY VIRUSES
WHALES CAN GET VIRUSES, TOO
EVERYTHING IN BETWEEN CAN BE INVADED BY VIRUSES BUT NOTHING INFECTS VIRUSES—NOTHING IS SMALL ENOUGH.
THEY ARE KNOWN TO BE THE MOST NUMEROUS TYPE OF LIFE, BECAUSE THERE ARE AN ESTIMATED 10-100 VIRIONS FOR EACH INDIVIDUAL BACTERIUM (WEINBAUER 2004).
IN ADDITION, THERE ARE MULTIPLE VIRIONS FOR ALL THE OTHER TYPES OF LIFE-FORMS AS WELL.
THEY EXIST IN MIND-BOGGLING NUMBERS. THE NUMBER OF VIRUSES ON THE PLANET HAS BEEN ESTIMATED TO BE OVER
10,000,000,000,000,000,000,000,000,000,000! PEDULLA 2003
10
31
VIRUSES
THEY ARE THE MOST ABUNDANT LIFE-FORMS ON EARTH, BY AT LEAST A FACTOR OF TEN.
10³¹ VIRUSES WORKS OUT TO 20,000 VIRIONS FOR EVERY SQUARE MICRON OF THE EARTH’S SURFACE.
7 MICRONS
4 MICRONS 20K
20K
20K
20K
20K
20K
20K
20K
20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K
20K
20K
20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K
20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K 20K
20K
E. COLI 20K
20K 20K
20K 20K
20K 20K
20K 20K
20K 20K
20K 20K
20K
20K
20K
20K
20K
20K
20K
20K
RED BLOOD CELL
20K
20K
20K
20K
20K
20K
20K 20K
20K
20K
20K 20K
20K
20K 20K
20K
20K 20K 20K
20K 20K 20K
20K 20K
THERE ARE AN ESTIMATED
10²⁵ VIRAL INFECTIONS OF CELLS EVERY SECOND, WORLDWIDE (PEDULLA 2003).
10,000,000,000,000,000,000,000,000/SECOND
THE ATOMIC CLOCK IS THE OFFICIAL STANDARD OF TIME; IT’S BASED ON THE PRECESSIONS OF THE CESIUM ATOM. THE CESIUM ATOM PRECESSES, OR “TICKS”, 9,192,631,770 TIMES PER SECOND. THERE ARE ONE MILLION BILLION (10¹⁵) VIRAL INFECTIONS FOR EVERY CESIUM “TICK”.
PART III: THE CAPSID
QUESTION: WHAT IS THE FIRST NEED OF ALL LIVING THINGS…INCLUDING VIRUSES?
?
?
?
?
THE FIRST NEED OF ALL LIVING THINGS IS TO PHYSICALLY ENCAPSULATE THEIR GENOME.
NUCLEIC ACIDS ARE SUBJECT TO ATTACK FROM MANY THINGS IN THE ENVIRONMENT; THEY NEED TO BE PROTECTED.
THE MAJORITY OF VIRAL GENOMES ARE MADE OF RNA, A MOLECULE VERY SIMILAR TO DNA. RNA IS MUCH MORE SENSITIVE TO ATTACK THAN DNA, BECAUSE OF AN ADDITIONAL HYDROXYL GROUP (—OH GROUP, ARROW) ATTACHED TO THE SUGAR MOLECULE. THINK OF THE HYDROXYL GROUP AS A RIPCORD FOR DISMANTLING THE RNA. VIRUSES NEED TO PROTECT THEIR GENOMES WITH GREAT CARE. HOW DO THEY DO THIS?
THEY PROTECT THEIR GENOME WITH A PROTEIN COAT, OR CAPSID. THIS IS A TOUGH JACKET THAT KEEPS THE DNA or RNA SAFE FROM ENVIRONMENTAL FACTORS…CHEMICALS, ULTRAVIOLET LIGHT, ETC.
CAPSID TYPES THERE ARE 3 MAJOR TYPES OF BODY PLAN FOR VIRAL CAPSIDS:
1. RODS 2. FILAMENTS 3. ICOSAHEDRONS ALL OF THESE CONFIGURATIONS SERVE THE SAME DNA/RNA PROTECTIVE FUNCTION. THE MAJORITY OF VIRUSES ARE ICOSAHEDRAL. THEY WILL BE THE MAIN FOCUS OF THIS WORK.
RODS RNA
PROTEIN SUBUNITS
ROD VIRUSES ARE STRAIGHT. THEY CONSIST OF A SPIRAL OF SINGLE-STRANDED NUCLEIC ACID, WITH PROTEIN SUBUNITS ATTACHED TO THE OUTSIDE. THIS IS TOBACCO MOSAIC VIRUS (TMV). see KLUG 1999B
THE ARCHITECTURE OF TMV IS LIKE A BRICK CHIMNEY (MINUS THE BIRDS).
FILAMENTS FILAMENT VIRUSES ARE LONGER, THINNER, AND WHIP-LIKE. THEY MAKE NO ATTEMPT TO BE STRAIGHT.
THIS IS BEET YELLOWS VIRUS, SIMILAR TO M-13.
AGRANOVSKY 1995
FILAMENTS HAVE THE SAME BASIC DESIGN AS THE RODS: A SPRINGSHAPED COIL OF NUCLEIC ACID, COVERED WITH PROTEIN SUBUNITS. THIS IS A CLOSE-UP OF M-13. ITS CAPSID PROTEIN CONSISTS OF JUST A THIN STRAND CALLED AN ALPHA HELIX, HERE REPRESENTED BY INDIVIDUAL CYLINDERS. ITS SINGLE-STRANDED DNA IS SHOWN INSIDE. see BHATTACHARJEE 1992
ICOSAHEDRONS
see KRONENBERG 2005, FIG. 2
THE ICOSAHEDRON IS BASICALLY A SPHERICAL SHAPE. SMALLER VIRUSES GENERALLY CONSIST OF JUST NUCLEIC ACID WRAPPED IN A PROTEIN CAPSID.
THE ICOSAHEDRAL VIRUS IS A SIMILAR IN DESIGN TO A BLACKBERRY: SMALL BLOBS OF MATERIAL SURROUNDING A CORE.
AN ICOSAHEDRON IS A THREE-DIMENSIONAL GEOMETRIC SHAPE WITH 20 TRIANGULAR FACETS.
IT HAS 12 POINTS, OR VERTICES:
NATURE UNDOUBTEDLY CHOSE THE ICOSAHEDRON BECAUSE IT’S A PLATONIC SOLID: IN OTHER WORDS, THE ANGLES ARE ALL THE SAME. THIS SIMPLIFIES THE DESIGN, AND MAKES SELF-ASSEMBLY POSSIBLE.
~222°
~222°
~222°
AN ICOSAHEDRON HAS A 5-FACETED CAP ON THE TOP AND BOTTOM, AND A 10-FACETED GIRDLE.
THE SIMPLEST ICOSAHEDRAL VIRUSES HAVE 60 PROTEIN SUBUNITS, 3 FOR EACH OF THE FACETS. THIS GIVES 3 POINTS TO DEFINE EACH TRIANGLE.
THIS IS SATELLITE PANICUM MOSAIC VIRUS (SPMV); IT’S THE SMALLEST ICOSAHEDRAL VIRUS. IT HAS JUST 60 PROTEIN SUBUNITS, CALLED CAPSID PROTEINS (CPs). IT IS ONLY 16 NANOMETERS IN DIAMETER—THAT’S REALLY SMALL, EVEN FOR A VIRUS (BAN 1995).
EXTERNAL VIEW
INTERNAL VIEW
IN THIS INTERNAL VIEW, IT’S EASY TO SEE THAT THERE ARE 3 PROTEINS TO DEFINE EACH TRIANGULAR FACET.
PART IV: CODING SPACE
11.4 NM
SPMV HAS AN INTERNAL DIAMETER OF 11.4 NANOMETERS (BAN 1995). THIS GIVES IT AN INTERNAL VOLUME OF 775 CUBIC NANOMETERS (NM³), OR 775,000 CUBIC ANGSTROMS (ų).
THE ANGSTROM (Å) IS A SPECIALIZED UNIT OF MEASURE. IT IS EQUAL TO 100 PICOMETERS, OR 1/10TH OF A NANOMETER. IT IS USED LARGELY TO MEASURE THE LENGTH OF BONDS BETWEEN ATOMS.
THIS IS THE RELATIONSHIP BETWEEN ANGSTROMS AND NANOMETERS: DISTANCE:
AREA: VOLUME:
IMAGINE, THAT A FRIEND CALLS YOU UP IN THE MIDDLE OF THE NIGHT, AND TELLS YOU THAT SOMEONE HAS DISCOVERED A NEW ICOSAHEDRAL VIRUS THAT IS ONLY 5 NANOMETERS IN DIAMETER. THIS WOULD BE DWARFED BY SPMV, WHICH IS ABOUT AS TINY AS ANY VIRUS CAN GET.
SPMV, 16 NM
AIN’T GONNA’ HAPPEN VIRUS (AGHV), 5 NM
YOU SAY, “ROLL OVER AND GO BACK TO SLEEP!”...THIS IS THE CORRECT RESPONSE.
A VIRUS OF THIS SIZE SIMPLY CAN’T EXIST, AND NOW WE’LL SEE WHY. THE ISSUE IS CODING SPACE: THE AMOUNT OF PHYSICAL SPACE NEEDED FOR ITS GENETIC CODE.
OH
A SINGLE BASE OF DNA (OR RNA) TAKES UP ABOUT 700 CUBIC ANGSTROMS (700 ų, OR 0.7 NM³) OF PHYSICAL SPACE.
SPMV’s 775,000 ų OF INTERNAL SPACE, DIVIDED BY 700 ų PER BASE, GIVES IT A MAXIMUM POSSIBLE GENOME OF 1,107 BASES. SPMV’s ACTUAL GENOME HAS 824 BASES OF RNA.
NOTICE, THAT CAPSIDS AREN’T COMPLETELY FILLED UP WITH NUCLEIC ACID.
BAKER 1988, FIG. 3
SPMV’s CAPSID PROTEIN HAS 157 AMINO ACIDS. 157 x 3 = 471 BASES. SUBTRACT 471 BASES FROM THE 824 IN ITS’ GENOME, AND THERE ARE JUST 353 BASES LEFT.
157 AMINO ACIDS
see QIU 2001
SPMV GENOME
THIS IS THE SPMV GENOME. THE CAPSID PROTEIN (MARKED “CP”) TAKES UP MORE THAN HALF. THERE IS ONLY ROOM FOR ONE SMALL EXTRA PROTEIN. THERE ARE JUST 824 RNA BASES IN THE ENTIRE GENOME. THIS IS THE SMALLEST VIRAL GENOME.
VIRUSES CAN’T BE ANY SMALLER. IF THEY WERE, THEY WOULD RUN OUT OF SPACE FOR THEIR OWN DNA.
SO, LET’S LOOK ONCE AGAIN AT THE CASE OF AGHV (“AIN’T GONNA’ HAPPEN VIRUS”).
SPMV, 16 NM
AIN’T GONNA’ HAPPEN VIRUS (AGHV), 5 NM
LET’S PRETEND THAT THE ENTIRE PHYSICAL SPACE OF THE VIRUS IS MADE UP OF NUCLEIC ACID. OF COURSE ROOM IS NEEDED FOR THE PROTEIN SUBUNITS, BUT WE’LL IGNORE THAT FOR THE MOMENT.
5 NM
A SPHERE OF 5 NM DIAMETER HAS ~65 NM³ OF PHYSICAL VOLUME.
65 / 0.7 = 93 POSSIBLE DNA or RNA BASES. DIVIDE 93 BY 3, AND IT WILL PROVIDE CODING FOR JUST 31 AMINO ACIDS…AND THAT LEAVES NOTHING IN THE GENOME FOR ANY KIND OF GENE PROMOTER, NOR ANY SPACE BETWEEN THE NUCLEIC ACID AND THE PROTEIN COAT.
SPMV GENOME
AGHV GENOME (HYPOTHETICAL)
31 AMINO ACIDS IS TOO SMALL TO FORM ANY KNOWN TYPE OF CAPSID PROTEIN. A 5 NM VIRUS WOULD BE TOO SMALL TO HOLD ENOUGH DNA TO FORM THE PROTEIN TO COVER ITSELF. THE 5 NANOMETER ICOSAHEDRAL VIRUS IS PHYSICALLY IMPOSSIBLE.
31 AA PROTEIN
157 AA CAPSID PROTEIN (SMALLEST KNOWN OF THIS TYPE)
MORAL OF THE STORY: VIRUSES ARE AS SMALL AS THEY ARE, BECAUSE THEY CAN’T BE ANY SMALLER. IF THEY COULD BE SMALLER, THEY WOULD. NATURE HAS FILLED UP EVERY POSSIBLE ECOLOGICAL NICHE, WITH SOME SORT OF LIFE-FORM.
PART V: GENOME ENVY
A HUMAN BEING HAS ~24,000 GENES. THE SPMV GENOME HAS JUST 2 GENES. THIS IS WHY VIRUSES DON’T HAVE TEETH.
HUMAN GENOME (~24,000 GENES)
SPMV GENOME (2 GENES)
MORE SPACE
=
LONGER GENOME
= GREATER COMPLEXITY …SIZE DOES MATTER!
SMALL VIRUSES HAVE DREAMS AT NIGHT, ABOUT ALL THE THINGS THEY WOULD BE IF THEY HAD MORE SPACE FOR THEIR GENOME. THEY CRAVE THE GREATER COMPLEXITY OF LARGER ORGANISMS.
Z
?
SO, HOW DOES A VIRUS INCREASE ITS INTERNAL VOLUME, AND CODING CAPACITY?
THERE ARE 2 WAYS TO MAKE MORE SPACE FOR THE GENOME: 1. A BIGGER CAPSID PROTEIN 2. MORE CAPSID PROTEINS
BIGGER CPs SPMV HAS 60 COPIES OF A 157-AMINO ACID CAPSID PROTEIN, WHICH CREATES A CAPSID WITH AN INTERNAL VOLUME OF 775 NM³.
18 NM
13.6 NM BAN 1995
THIS IS SATELLITE TOBACCO NECROSIS VIRUS (STNV). IT HAS 60 COPIES OF A 196-AMINO ACID CAPSID PROTEIN. THIS GIVES IT AN INTERNAL VOLUME OF 1,317 NM³.
60 COPIES SPMV CP, 157 AAs
SPMV, 775 NM³ 70 % INCREASE
25 % INCREASE
60 COPIES STNV CP, 196 AAs
STNV, 1317 NM³
STNV’S CP HAS 196 AMINO ACIDS—THAT’S 25% MORE THAN SPMV’S 157. BUT, STNV ALSO HAS 1,317 NM³ OF INTERNAL SPACE—THAT’S 70% MORE THAN SPMV’S 775 NM³. THIS GIVES MORE GENOME SPACE, OUT OF PROPORTION TO THE INCREASE IN THE CODING NEEDED FOR THE BIGGER PROTEIN. THIS ALLOWS FOR DIVERSIFICATION OF THE GENOME.
SO, INCREASING THE SUBUNIT SIZE IS A GOOD STRATEGY, TO A POINT. IT WORKS WELL WITH THE SATELLITE VIRUSES, WHICH HAVE VERY COMPACT CAPSID PROTEINS. THESE PROTEINS HAVE ONLY AN “S” (SHELL) DOMAIN, THE MINIMUM NEEDED TO ENCASE THE GENOME.
S
THE “S” DOMAIN IS WHAT SPACECRAFT DESIGNERS WOULD CALL THE “PRESSURE SHELL”: THE CASING THAT PROTECTS THE LIFE INSIDE.
S
MANY OTHER VIRAL CAPSID PROTEINS ALSO HAVE A “P” (PROJECTING) DOMAIN, WHICH PROTRUDES OUTSIDE THE VIRUS. A NUMBER OF THEM ALSO HAVE AN “R” (RNA-ASSOCIATING) DOMAIN THAT PROJECTS INSIDE, AND MINGLES WITH THE NUCLEIC ACID.
P
S R
THE “P” AND “R” DOMAINS REQUIRE MORE CODING SPACE, BUT THEY DON’T CONTRIBUTE TO THE INTERNAL SPACE OF THE CAPSID. HERE IS ONE SUCH VIRAL CP WITH THESE DOMAINS, TOMATO BUSHY STUNT VIRUS (TBSV):
P
P DOMAIN
S
S DOMAIN
R
R DOMAIN see HSU 2006, FIG. 1
THIS IS CANINE PARVOVIRUS (CPV). ITS CAPSID CONSISTS OF 60 COPIES OF A 584-AMINO ACID PROTEIN. BY LOOKING AT ITS JAGGED TOPOGRAPHY, ONE MAY SUSPECT THAT ITS CAPSID PROTEIN HAS A PROJECTING DOMAIN.
THIS IS THE CPV CAPSID PROTEIN. AT THE CORE, IT’S THE SAME 8-BETA STRAND PROTEIN AS MOST OF THE OTHER ICOSAHEDRONS. THE 8 STRANDS ARE SHOWN HERE, NUMBERED “B” THROUGH “I”.
CPV CAPSID PROTEIN see XIE 1996
GENERIC 8-STRANDED CAPSID PROTEIN see JOHNSON 1996
BUT CPV’s PROTEIN IS ALSO EXTREMELY BLOATED, WITH LONG INSERTIONS. THIS IS WHY THE CPV CAPSID HAS SUCH A LUMPY APPEARANCE.
CPV CAPSID PROTEIN see XIE 1996
60 COPIES SPMV, 775 NM³
SPMV CP, 157 AAs
272% INCREASE
232% INCREASE
60 COPIES
CPV CP, 584 AAs
CPV, 2,570 NM³
CPV’S CAPSID PROTEIN IS 272% LARGER THAN THAT OF SPMV. BUT CPV’S INTERNAL SPACE IS ONLY 232% GREATER THAN SPMV’s. THE REASON IS THE LARGE AMOUNT OF CP MATERIAL THAT DOESN’T CONTRIBUTE TO THE SHELL. CLEARLY, THIS STRATEGY OF INCREASING THE SUBUNIT SIZE IS PRONE TO FAILURE.
?
SO, THE NEXT QUESTION IS, CAN I DO BETTER BY INCREASING THE NUMBER OF CAPSID PROTEINS?...AND, HOW IS THAT GOING TO WORK? WILL THESE PROTEINS KNOW HOW TO ORGANIZE THEMSELVES? WILL THEY ALL JUST FALL TOGETHER…OR WILL THEY REQUIRE SOME SORT OF HELP?
EVERY ICOSAHEDRAL VIRUS HAS 60 ICOSAHEDRAL ASYMMETRIC UNITS (IAUs). THESE ARE 60 ZONES ON THE CAPSID (THE INDIVIDUAL TRAPEZOIDS) THAT ARE PHYSICALLY AND CHEMICALLY IDENTICAL TO EACH OTHER.
THE SIMPLEST TYPE OF ICOSAHEDRAL VIRUSES, SUCH AS SPMV, HAVE JUST ONE PROTEIN FOR EACH IAU—60 PROTEINS TOTAL. THIS TYPE IS SAID TO HAVE A TRIANGULATION NUMBER (T-NUMBER) OF 1.
T=1
see ROSSMANN 1989, FIG. 2
IN A T=1 VIRUS, ALL OF THE PROTEIN SUBUNITS EXIST IN PRECISELY THE SAME TYPE OF BIOCHEMICAL ENVIRONMENT—THAT IS, THEY’RE ALL SURROUNDED BY EXACTLY THE SAME PARTS OF OTHER PROTEINS.
THIS IS THE SPMV CAPSID PROTEIN. IT HAS BEEN DEMARCATED ARBITRARILY INTO 9 ZONES.
THIS IS THE SPMV CAPSID PROTEIN SURROUNDED BY OTHER SUBUNITS. NOTICE THAT ZONE 1 IS ALWAYS NEAR ZONE 9 (ON THE ADJOINING SUBUNIT), 3 IS NEAR 4, 5 IS BETWEEN 2 AND 8, AND 6 IS NEAR 7. THESE ARRANGEMENTS ARE CONSISTENT OVER THE ENTIRE CAPSID.
T=3
IN VIRUSES WITH T-NUMBERS HIGHER THAN 1, THERE IS MORE THAN ONE PROTEIN IN EACH IAU. THIS IS A T=3 VIRUS, SO IT HAS 3 PROTEINS (COLORED BLUE, GREEN, AND RED) IN EACH IAU (HEAVY LINES). BELOW IS THE IAU FOR TOMATO BUSHY STUNT VIRUS (TBSV). IT HAS 3 COPIES OF ITS CAPSID PROTEIN THAT ARE IDENTICAL, IN TERMS OF AMINO ACID SEQUENCE.
see ROSSMANN 1989, FIG. 2
HOWEVER, THE 3 PROTEINS HAVE SLIGHT PHYSICAL DIFFERENCES FROM EACH OTHER:
A
B C
B
SEEN IN CROSS-SECTION, THE BLUE (A) SUBUNIT HAS A PARTICULAR DISPOSITION COMPARED TO THE RED (B) SUBUNIT.
C A THE DISPOSITION OF THE RED (B) SUBUNIT VERSUS THE GREEN (C) IS DIFFERENT FROM THE OTHER TWO.
THE DISPOSITION OF THE GREEN (C) AGAINST THE BLUE (A) IS DIFFERENT— THE DIFFERENCE IS SMALL, BUT MEANINGFUL.
WHEN THERE ARE MORE THAN ONE PROTEIN IN AN IAU, THESE PROTEINS SORT THEMSELVES INTO SLIGHTLY DIFFERENT ARRANGEMENTS WITH EACH OTHER. EACH PROTEIN IN AN IAU HAS ITS OWN SPECIAL BIOCHEMICAL ENVIRONMENT, THAT IS, ITS PHYSICAL DISPOSITION PERTAINING TO THE OTHER PROTEINS.
THE SUBUNITS ADAPT TO THESE DIFFERING BIOCHEMICAL ENVIRONMENTS BY ADOPTING SLIGHTLY DIFFERENT PHYSICAL SHAPES, OR CONFORMATIONS.
A
B
C THIS IS THE IAU OF TBSV. IT HAS 3 PROTEINS (LETTERED “A” THROUGH “C”) IN EACH IAU, EACH WITH A SLIGHTLY DIFFERENT PHYSICAL SHAPE. SOME OF THE DIFFERENCES ARE SHOWN HERE. BECAUSE THESE CONFORMATIONS ARE EXTREMELY SIMILAR BUT NOT IDENTICAL, THEY’RE SAID TO BE QUASI-EQUIVALENT.
MORE CPs THIS IS TOMATO BUSHY STUNT VIRUS (TBSV). ITS CAPSID IS MADE OF 180 COPIES OF A 388 AMINO ACID PROTEIN.
180 COPIES
60 COPIES
THE CAPSID HAS 60 IDENTICAL COPIES OF EACH OF 3 DIFFERENT CONFORMATIONS. EVERY IAU HAS ONE OF EACH OF THESE 3 CONFORMATIONS.
T=3
T=1
TBSV HAS A TRIANGULATION NUMBER (TNUMBER) OF 3. THIS MEANS THAT IT HAS 3 x 60 = 180 CAPSID SUBUNITS. IT ALSO MEANS THAT THERE ARE 3 DISTINCT CHEMICAL ENVIRONMENTS.
SPMV HAS A T-NUMBER OF 1. IT HAS JUST 1 x 60 = 60 SUBUNITS…ALL THESE SUBUNITS ADOPT PRECISELY THE SAME SHAPE, AND RELATE TO EACH OTHER THE SAME WAY.
TBSV’s CAPSID SUBUNIT HAS 388 AMINO ACIDS. THAT’S 2.5 TIMES SPMV’s 157 AMINO ACIDS. BUT TBSV’s 5,500 NM³ OF INTERNAL VOLUME IS 7.1 TIMES THE 775 NM³ OF SPMV. IT ACHIEVES THIS BY ARRANGING ITS CAPSID PROTEINS INTO THOSE 3 DIFFERENT CHEMICAL ENVIRONMENTS.
(TO SCALE)
TBSV HAS ~4,800 RNA NUCLEOTIDES, AND 5 PROTEIN CODING GENES (NCBI.NLM.NIH.GOV).
THIS IS CAULIFLOWER MOSAIC VIRUS (CaMV). IT’S A T=7 ICOSAHEDRON.
see CHENG 1992
ITS CAPSID IS MADE OF 420 COPIES (7 x 60) OF A 490 AMINO ACID PROTEIN. EACH ONE OF THE LITTLE “VOLCANOES” ON ITS SURFACE CONSISTS OF EITHER 5 OR 6 COPIES OF THIS PROTEIN. EACH OF ITS IAUs HAS 7 CAPSID SUBUNITS.
THIS GIVES CaMV ~14,000 NM³ OF INTERNAL VOLUME.
see CHENG 1992
ITS GENOME HAS ~8,000 NUCLEOTIDES, AND 7 PROTEIN CODING GENES--11 GENES TOTAL (NCBI.NLM.NIH.GOV).
CaMV HAS A CAPSID PROTEIN WITH 490 AMINO ACIDS, 3.1 TIMES THE 157 AMINO ACIDS OF SPMV. BUT THE 14,000 NM³ OF INTERNAL VOLUME IN CaMV IS 18.1 TIMES THE 775 NM³ INTERNAL SPACE OF SPMV. THIS IS MADE POSSIBLE BY THE 7 DIFFERENT BONDING ENVIRONMENTS OF ITS CAPSID PROTEINS.
(TO SCALE)
T=1
T=7
IN A T=7 VIRUS, THE 7 SUBUNITS IN AN IAU EACH TAKE A DIFFERENT PHYSICAL SHAPE.
THESE ARE IDEALIZED ICOSAHEDRAL FACETS FOR (FRAMES 1 THROUGH 3) T=4, T=7, & T=13 CAPSIDS. THEIR QUASI-EQUIVELANT SUBUNITS ARE LABELLED “A” THROUGH “D” (FRAME 1), “A” THROUGH “G” (FRAME 2), AND “A” THROUGH “M” (FRAME 3). NOTICE THAT THE FACETS ARE ANCHORED ON EACH CORNER BY A PENTAGON—THAT’S THE VERTEX. T=4 1
T=7 2
see THUMAN-COMMIKE 1998B, FIG. 6
T = 13 3
INCIDENTALLY, NOT ALL CAPSIDS USE THE SAME PROTEIN FOR THEIR CONSTRUCTION. ONE SUCH CASE IS POLIO, WHICH HAS 60 COPIES EACH OF 3 DIFFERENT MAJOR CAPSID PROTEINS.
VP1, 306 AAs 60 COPIES
VP2, 272 AAs 60 COPIES
VP3, 238 AAs 60 COPIES
see HOGLE 1985, FIG. 3
FOR THIS REASON, POLIO IS KNOWN AS A PSEUDO T=3, OR P=3 VIRUS. THE SUBUNIT ARRANGEMENT IS ON THE RIGHT: WHITE LINES SHOW IAUs, AND YELLOW LINES SHOW THE SUBUNIT POSITIONS.
see HARBER 1995, FIG. 1
THESE CAPSIDS RANGE FROM T=1 TO T=25. NOTICE THAT AS THE T-NUMBERS INCREASE, SO DO THE PHYSICAL SIZE AND COMPLEXITY OF THE CAPSIDS.
T=1 T=3 T=7
T = 13 T = 25 see JOHNSON 1997, FIG. 6
(ALL TO THE SAME SCALE)
THIS STRATEGY OF QUASI-EQUIVELANCE SEEMS TO BE WORKING WELL. HOW MUCH FURTHER CAN IT BE TAKEN?
THIS IS PBCV-1, A VIRUS OF PROTOZOANS. ITS TNUMBER IS 169. IT’S CONSIDERED LARGE FOR A VIRUS; IT’S 190 NM IN DIAMETER. SPMV IS SHOWN BESIDE IT FOR COMPARISON.
NANDHAGOPAL 2002, FIG. 1A
YOU’D EXPECT PBCV-1 TO HAVE 60 x 169 = 10,140 CAPSID PROTEINS. CORRECT, BUT THIS TIME IT WORKS DIFFERENTLY. THIS IS THE MAIN CP FOR PBCV-1, CALLED VP-54. THE CAPSID HAS 5,040 COPIES OF THIS PROTEIN, JUST UNDER HALF THE EXPECTED NUMBER. HOWEVER, THIS PROTEIN HAS 2 MAJOR DOMAINS (SHOWN HERE AS RED AND GREEN); IN THIS PARTICULAR CASE, THE 2 DOMAINS FUNCTION STRUCTURALLY AS IF THEY WERE 2 SEPARATE PROTEINS. BUT THAT STILL DOESN’T ACCOUNT FOR THE FULL 10,140…WHERE’S THE REST OF THEM?
NANDHAGOPAL 2002, FIG. 3
THE OTHER PROTEINS ARE FOUND AT EACH VERTEX. REMEMBER, EVERY ICOSAHEDRON HAS 12 VERTICES. EACH VERTEX HAS 5 COPIES OF A DIFFERENT PROTEIN. THIS IS HOW THE CAPSID HAS THE FULL 10,140 PROTEINS. (NANDHAGOPAL 2002).
EACH VERTEX HAS A CONFIGURATION THAT LOOKS LIKE THIS:
see VAN ETTEN 1999, FIG. 1F
5,040 VP54 PROTEINS, x 2 DOMAINS = 10,080 CPs
+ 12 x 5 = 60 VERTEX CPs
T-NUMBER:
=
10,140 CPs
169 60 10,140
PBCV-1 HAS ~330,000 BASE PAIRS OF DNA, AND ~375 PROTEIN ENCODING GENES (NANDHAGOPAL 2002). ITS GENOME COMPLEXITY APPROACHES THAT OF SOME BACTERIA. IT HAS ~2,000 TIMES AS MUCH INTERNAL VOLUME AS SPMV.
see VAN ETTEN 1999, FIG. 1 (WITH MODIFICATIONS)
PBCV-1 HAS ENOUGH INTERNAL SPACE FOR SPMV TO PURSUE VARIOUS RECREATIONAL ACTIVITIES INSIDE OF IT.
THIS IS WORKING GREAT! I WANT MORE!
MIMIVIRUS IS THE LARGEST KNOWN ICOSAHEDRAL. IT IS 500 NM IN DIAMETER (ONE-HALF OF A MICRON).
see XIAO 2005
IT’S TWICE AS LARGE AS ANY OTHER KNOWN VIRUS. ITS TNUMBER HASN’T EVEN BEEN DETERMINED YET, THOUGH IT HAS BEEN ESTIMATED AT T = ~1,179 (XIAO 2005).
IT HAS 1.2 MILLION BASE PAIRS, AND 911 PROTEIN-CODING GENES. THIS MAKES IT MORE COMPLEX THAN SOME BACTERIA (PARTICULARLY THE MYCOPLASMA).
INSIDE DIAMETER 380 NM
OUTSIDE DIAMETER 500 NM
see XIAO 2005
THIS IS THE LARGEST KNOWN VIRAL GENOME. IT CODES FOR THINGS THAT NO OTHER VIRUS DOES, INCLUDING ENZYMES FOR DNA REPAIR, AND ENZYMES THAT ATTACH AMINO ACIDS TO TRANSFER RNA (SUZAN-MONTI 2006).
ONLY ABOUT 300 OF THE MIMIVIRUS GENES HAVE A KNOWN FUNCTION (SUZAN-MONTI 2006). TRANSLATION tRNA MODIFICATION R663 L124 L164 R639 R726 R624 R464 L496 R405
ARG-tRNA SYNTHETASE TYR-tRNA SYNTHETASE CYS-tRNA SYNTHETASE MET-tRNA SYNTHETASE RELEASE FACTOR eRF1 ELONGATION FACTOR eF-Tu INITIATION FACTOR SUI1 INITIATION FACTOR 4E tRNA (5-URACIL-) METHYLASE
L359 R693 R406 L315, L720 R194, L221 R480 L687 L469
MISMATCH REPAIR ATPase MutS METHYLATED-DNA-PROTEIN-METHYLTRANSFERASE DIOXYGENASE ALKYLATED DNA REPAIR FORMAMIDOPYRIMIDINE DNA GLYCOSYLASE TOPOISOERASE IB, IA TOPOISOMERASE IIA ENDONUCLEASE UV-DAMAGED DNA REPAIR POLYNUCLEOTIDE KINASE-PHOSPHATASE
L254, L393 R260,R266,R445 L605 L251
HSP70 DNAJ-LIKE PROTEINS PEPTIDYL-PROLYL ISOMERASE LON-LIKE PROTEASE
NUCLEOTIDE SYNTHESIS R418 L716
AMINO ACID METABOLISM R475 R565
ASPARAGINE SYNTHASE GLUTAMINE SYNTHASE
L230
LYSYL HYDROXYLASE
L906 L808 R807
CHOLINESTERASE LANOSTEROL-14-ALPHA-DEMETHYLASE DEHYDROCHOLESTEROL REDUCTASE
PROTEIN MODIFICATION
DNA REPAIR
PROTEIN FOLDING
NUCLEOSIDE DIPHOSPHATE KINASE GMP SYNTHASE
LIPID METABOLISM
POLYSACCHARIDE METABOLISM R689 L136 L780 L612 L543
NAG-1-PHOSPHATE URIDYLYLTRANSFERASE SUGAR TRANSAMINASE REDUCTASE MANNOSE-6-PHOSPHATE ISOMERASE ADP-RIBOSYLGLYCOHYDROLASE
AMONG KNOWN VIRUSES, THE GENES ON THIS PAGE ARE UNIQUE TO MIMIVIRUS (see SUZAN-MONTI 2006)
MIMIVIRUS IS GIGANTIC COMPARED TO SPMV, ABOUT 30 TIMES ITS SIZE. THIS IS ROUGHLY THE SAME SIZE RELATIONSHIP AS AN ELEPHANT AND A HAMSTER.
!!!
INCIDENTALLY, IT TAKES JUST 6 INCREASES OF ~30 TIMES IN SIZE TO ENCOMPASS MOST OF THE LIVING THINGS ON EARTH.
EACH ONE OF THE GREEN ARROWS REPRESENTS AN INCREASE ON THE LONGEST DIMENSION OF ~30 TIMES.
SPMV, 16 NM
WHALE, 15 METERS
FLEABAG, 450 MM
MIMIVIRUS, 500 NM
VORTICELLA, 15 MICRONS
ROTIFER, 450 MICRONS
WASP, 15 MM
SO, HOW BIG CAN A VIRUS GET? NOBODY KNOWS. THERE IS NO KNOWN UPWARD LIMIT ON THE SIZE OF A VIRUS (CLAVERIE 2006).
JUST YOU WAIT! I’LL BE BACK, AND I’LL HAVE MORE GENES THAN YOU!!
AS SPMV WALKS AWAY INTO THE SUNSET, HE HAS HAPPY DREAMS ABOUT HIS BIG GENOME FUTURE.
MAYBE WE’LL SEE HIM AGAIN SOMEDAY. MAYBE HE’LL HAVE TEETH.
METHODS VIRAL INTERNAL VOLUMES WERE COMPUTED USING THE FORMULA FOR A SPHERE: R³ x (4/3π). INTERNAL DIAMETERS WERE OBTAINED FROM LITERATURE SOURCES CITED, OR DIRECT MEASUREMENT OF VIRAL IMAGES.
IMAGES THROUGHOUT THIS WORK, VIRAL IMAGES WERE USED THAT WERE OBTAINED FROM THE WEBSITE OF THE SCRIPPS RESEARCH INSTITUTE (TSRI), SPECIFICALLY THEIR VIPER (VIRUS PARTICLE EXPLORER) DATABASE. ELECTRON MICROSCOPE, DIAGRAM: PURDUE.EDU ICOSAHEDRON: GEOM.UIUC.EDU LOBSTER CLAWS: GEORGIACOUNCIL.BLOGSPOT.COM GOLDEN EAGLE CLAWS: FLORIDA CENTER FOR INSTRUCTIONAL TECHNOLOGY (FCIT), ETC.USF.EDU VARIOUS IMAGES WERE USED FROM WIKIMEDIA COMMONS. IN ADDITION, I CREATED ORIGINAL ARTWORK USING ADOBE ILLUSTRATOR, PHOTOSHOP, MICROSOFT PAINT, AND MICROSOFT POWERPOINT DRAWING OBJECTS.
TECHNICAL REFERENCES AGRANOVSKY 1995—AGRANOVSKY, ALEXEY A.; LESEMANN, DIETRICH E.; MAISS, EDGAR; HULL, ROGER & ATABEKOV, JOSEPH G. 1995. “RATTLESNAKE” STRUCTURE OF A FILAMENTOUS PLANT RNA VIRUS BUILT OF TWO CAPSID PROTEINS. PROC. NATL. ACAD. SCI. USA (BIOCHEMISTRY) VOL. 92, PP. 2470-73. BAKER 1988—BAKER, TIMOTHY S.; DRAK, JACQUELINE & BINA, MINOU. 1988.. RECONSTRUCTION OF THE THREE-DIMENSIONAL STRUCTURE OF SIMIAN VIRUS 40 AND VISUALIZATION OF THE CHROMATIN CORE. PROC. NATL. ACAD. SCI. USA (BIOPHYSICS) VOL. 85, PP. 422-26. BAKER 1999—BAKER, T. S.; OLSON, N. H. & FULLER, S. D. 1999. ADDING THE THIRD DIMENSION TO VIRUS LIFE CYCLES: THREE-DIMENSIONAL RECONSTRUCTION OF ICOSAHEDRAL VIRUSES FROM CRYO-ELECTRON MICROGRAPHS. MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS VOL. 63, NO. 4, PP. 862-922. BAN 1995—BAN, NENAD; LARSON, STEVEN B. & McPHERSON, ALEXANDER. 1995. STRUCTURAL COMPARISON OF THE PLANT SATELLITE VIRUSES. VIROLOGY 214, PP. 571-83. BHATTACHARJEE 1992—BHATTACHARJEE , S.; GLUCKSMAN, M.J. & MAKOWSKI, LEE. 1992. STRUCTURAL POLYMORPHISM CORRELATED TO SURFACE CHARGE IN FILAMENTOUS BACTERIOPHAGES. BIOPHYSICAL JOURNAL VOL. 61, MARCH 1992, PP. 725-735. CHANG 1992—CHANG, SHWU-FEN; SGRO, JEAN-YVES & PARRISH, COLIN R. 1992. MULTIPLE AMINO ACIDS IN THE CAPSID STRUCTURE OF CANINE PARVOVIRUS COORDINATELY DETERMINE THE CANINE HOST RANGE AND SPECIFIC ANTIGENIC AND HEMAGGLUTINATION PROPERTIES. JOURNAL OF VIROLOGY VOL. 66, NO. 12., PP. 6858-67. CHENG 1992—CHENG, R. H.; OLSON, N. H. & BAKER T. S. 1992. CAULIFLOWER MOSAIC VIRUS: A 420 SUBUNIT (T=7), MULTILAYER STRUCTURE. VIROLOGY 186(2), PP. 655-68. CLAVERIE 2006—CLAVERIE, JEAN-MICHEL; OGATA, HIROYUKI; AUDIC, STEPHANIE; ABERGEL, CHANTAL; SUHRE, KARSTEN & FOURNIER, PIERRE-EDOUARD. 2006. MIMIVIRUS AND THE EMERGING CONCEPT OF A “GIANT” VIRUS. VIRUS RESEARCH 117, PP. 133-44. FREDDOLINO 2006—FREDDOLINO, PETER L.; ARKHIPOV, ANTON S.; LARSON, STEVEN B.; McPHERSON, ALEXANDER & SCHULTEN, KLAUS. 2006. MOLECULAR DYNAMICS SIMULATIONS OF THE COMPLETE SATELLITE TOBACCO MOSAIC VIRUS. STRUCTURE 14, PP. 437-49.
TECHNICAL REFERENCES HARBER 1995—HARBER, JAMES; BERNHARDT, GÜNTER; LU, HUI-HUA; SGRO, JEAN-YVES; WIMMER, ECKARD. 1995. CANYON RIM RESIDUES, INCLUDING ANTIGENIC DETERMINANTS, MODULATE SEROTYPE-SPECIFIC BINDING OF POLIOVIRUSES TO MUTANTS OF THE POLIOVIRUS RECEPTOR. VIROLOGY 214, PP. 559-70. HOGLE 1985—HOGLE, J. M.; CHOW, M. & FILMAN, D. J. 1985. THREE-DIMENSIONAL STRUCTURE OF POLIOVIRUS AT 2.9 Å RESOLUTION. SCIENCE (NEW SERIES), VOL. 229, NO. 4720, PP. 1358-65. HSU 2006—HSU, CATHERINE; SINGH, PRATIK; OCHOA, WENDY; MANAYANI, DARLY J.; MANCHESTER, MARIANNE; SCHNEEMANN, ANETTE & REDDY, VIJAY S. 2006. CHARACTERIZATION OF POLYMORPHISM DISPLAYED BY THE COAT PROTEIN MUTANTS OF TOMATO BUSHY STUNT VIRUS. VIROLOGY 349, PP. 222-29. JOHNSON 1996—JOHNSON, JOHN E. 1996. FUNCTIONAL IMPLICATIONS OF PROTEIN-PROTEIN INTERACTIONS IN ICOSAHEDRAL VIRUSES. PROC. NATL. ACAD. SCI. USA VOL. 93, PP. 27-33. JOHNSON 1997—JOHNSON, JOHN E. & SPEIR, JEFFREY A. 1997. QUASI-EQUIVALENT VIRUSES: A PARADIGM FOR PROTEIN ASSEMBLIES. J. MOL. BIOL. 269, PP. 665-75. KELLER 1988—KELLER, BEAT; DUBOCHET, JACQUES; ADRIAN, MARC; MAEDER, MARLIES; WURTZ, MICHEL & KELLENBERGER, EDWARD. 1988. LENGTH AND SHAPE VARIANTS OF THE BACTERIOPHAGE T4 HEAD: MUTATIONS IN THE SCAFFOLDING CORE GENES 68 AND 22. JOURNAL OF VIROLOGY VOL. 62, NO. 8, PP. 2960-69. KLUG 1999B—KLUG, A. 1999. THE TOBACCO MOSAIC VIRUS PARTICLE: STRUCTURE AND ASSEMBLY. PHIL. TRANS. R. SOC. LOND. B 354, PP. 531-35. KRONENBERG 2005—KRONENBERG, STEPHANIE; BÖTTCHER, BETTINA; VON DER LIETH, KLAUS W.; BLEKER, SVENJA & KLEINSCHMIDT, JÜRGEN A. 2005. A CONFORMATIONAL CHANGE IN THE ADENO-ASSOCIATED VIRUS TYPE 2 CAPSID LEADS TO THE EXPOSURE OF HIDDEN VP1 N TERMINI. JOURNAL OF VIROLOGY VOL. 79, NO. 9, PP. 5296-5303. LEE 2006D—LEE, TAE-JIN & GUO, PEIXUAN. 2006. INTERACTION OF gp16 WITH pRNA AND DNA FOR GENOME PACKAGING BY THE MOTOR OF BACTERIAL VIRUS PHI29. J. MOL. BIOL. 356, PP. 589-99. NANDHAGOPAL 2002—NANDHAGOPAL, NARAYANASAMY; SIMPSON, ALAN A.; GURNON, JAMES R.; YAN, XIADONG; BAKER, TIMOTHY S.; GRAVES, MICHAEL V.; VAN ETTEN, JAMES L. & ROSSMANN, MICHAEL G. 2002. THE STRUCTURE AND EVOLUTION OF THE MAJOR CAPSID PROTEIN OF A LARGE, LIPID-CONTAINING DNA VIRUS. PNAS VOL. 99, NO. 23, PP. 14758-63.
TECHNICAL REFERENCES PEDULLA 2003—PEDULLA, MARISA L.; FORD, MICHAEL E.; HOUTZ, JENNIFER M. & 17 OTHER AUTHORS. 2003. ORIGINS OF HIGHLY MOSAIC MYCOBACTERIOPHAGE GENOMES. CELL VOL. 113, PP. 171-82. PORANEN 2004—PORANEN, MINNA M. & TUMA, ROMAN. 2004. SELF-ASSEMBLY OF DOUBLE-STRANDED RNA BACTERIOPHAGES. VIRUS RESEARCH 101, PP. 93-100. QIU 2001—QIU, WENPING & SCHOLTHOF, KAREN-BETH G. 2001. DEFECTIVE INTERFERING RNAs OF A SATELLITE VIRUS. JOURNAL OF VIROLOGY VOL. 75, NO. 11, PP. 5429-32. RAOULT 2004—RAOULT, DIDIER; AUDIC, STEPHANE; ROBERT, CATHERINE; ABERGEL, CHANTAL; RENESTO, PATRICIA; OGATA, HIROYUKI; LA SCOLA, BERNARD; SUZAN, MARIE & CLAVERIE, JEAN-MICHEL. 2004. THE 1.2 MEGABASE GENOME SEQUENCE OF MIMIVIRUS. SCIENCE VOL. 306, PP. 1344-50. ROSSMANN 1989—ROSSMANN, MICHAEL G. & JOHNSON, JOHN E. 1989. ICOSAHEDRAL RNA VIRUS STRUCTURE. ANNUAL REVIEW OF BIOCHEMISTRY, VOL. 58, PP. 533-73. SUZAN-MONTI 2006—SUZAN-MONTI, M.; LA SCOLA, B. & RAOULT, D. 2006. GENOMIC AND EVOLUTIONARY ASPECTS OF MIMIVIRUS. VIRUS RESEARCH 117, PP. 145-55. THUMAN-COMMIKE 1996—THUMAN-COMMIKE, PAMELA A.; GREENE, BARRIE; JAKANA, JOANITA; VENKATARAM PRASAD, B. V.; KING, JONATHAN; PREVELIGE, PETER E. Jr. & CHIU, WAH. 1996. THREEDIMENSIONAL STRUCTURE OF SCAFFOLDING-CONTAINING PHAGE P22 PROCAPSIDS BY ELECTRON CRYOMICROSCOPY. J. MOL. BIOL. 260, PP. 85-98. THUMAN-COMMIKE 1998—THUMAN-COMMIKE, PAMELA A.; GREENE, BARRIE; MALINSKI, JUSTINE A.; KING, JONATHAN & CHIU, WAH. 1998. ROLE OF THE SCAFFOLDING PROTEIN IN P22 PROCAPSID SIZE DETERMINATION SUGGESTED BY T=4 AND T=7 PROCAPSID STRUCTURES. BIOPHYSICAL JOURNAL VOL. 74, PP. 559-68. THUMAN-COMMIKE 1998B—THUMAN-COMMIKE, PAMELA A.; GREENE, BARRIE; MALINSKI, JUSTINE A.; BURBEA, MICHELLE; McGOUGH, AMY; CHIU, WAH & PREVELIGE, PETER E. JR. 1999. MECHANISM OF SCAFFOLDING-DIRECTED VIRUS ASSEMBLY SUGGESTED BY COMPARISON OF SCAFFOLDING-CONTAINING AND SCAFFOLDING-LACKING P22 PROCAPSIDS. BIOPHYSICAL JOURNAL VOL. 76, PP. 3267-77.
TECHNICAL REFERENCES VAN ETTEN 1999—VAN ETTEN, JAMES L. & MEINTS, RUSSELL H. 1999. GIANT VIRUSES INFECTING ALGAE. ANN. REV. MICROBIOL. VOL. 53, PP. 447-94. WEINBAUER 2004—WEINBAUER, MARKUS G. 2004. ECOLOGY OF PROKARYOTIC VIRUSES. FEMS MICROBIOLOGY REVIEWS 28, PP. 127-81. WOMMACK 2000—WOMMACK, ERIC K. & COLWELL, RITA R. 2000. VIRIOPLANKTON: VIRUSES IN AQUATIC ECOSYSTEMS. MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS VOL. 64, NO. 1., PP. 69-114. XIAO 2005—XIAO, CHUAN; CHIPMAN, PAUL R.; BATTISTI, ANTHONY J.; BOWMAN, VALORIE D.; RENESTO, PATRICIA; RAOULT, DIDIER & ROSSMANN, MICHAEL G. 2005. CRYO-ELECTRON MICROSCOPY OF THE GIANT MIMIVIRUS. J. MOL. BIOL. 353, PP. 493-96. XIE 1996—XIE, QING & CHAPMAN, MICHAEL S. 1996. CANINE PARVOVIRUS CAPSID STRUCTURE, ANALYZED AT 2.9 Å RESOLUTION. J. MOL. BIOL. 264, PP. 497-520.
I DID MOST OF THE WORK!
…AND DON’T FORGET JUGHEAD, MY HARD-WORKING RESEARCH ASSISTANT.
NOW, CUT THAT OUT!
