Proteins and symmetry - UF Macromolecular Structure …msg.mbi.ufl.edu/bch6746/lecture15.pdfViruses...
Transcript of Proteins and symmetry - UF Macromolecular Structure …msg.mbi.ufl.edu/bch6746/lecture15.pdfViruses...
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Proteins and symmetry
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Viruses (symmetry)
Viruses come in many shapes, sizes and compositionsAll carry genomic nucleic acid (RNA or DNA)
Structurally and genetically the simplest are the spherical viruses
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Purpose of protein viral capsid
AssemblySubunits must recognize each other to form a stable capsid (non-covalent interactions)>> self assemble
InfectionMust be able to transfer nucleic acid from one host to another>> stable and recognize receptor
Small genome
Genetic economy - few structural proteins symmetry - identical building blocks
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Simple Spherical Viruses
Protein
RNA/DNA
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From geometry considerations
Two 3D solid objects use a singlepoint symmetry operator toproduce the theoretical maximumpossible identical units to build a solid object
Icosahedron and
Dodecahedron
Identical symmetry (point group 5.3.2)
Enclose maximum volume
Icosahedron
Dodecahedron
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5-fold axis at each corner
3-fold at each face
Spherical Virus Shells have Icosahedral Symmetry-Built from 20 identicalequilateral triangles.
-Triangles are arranged toenclose the volume inside.
5 triangles
10 triangles
5 triangles2-fold at
each edge
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5-fold3-fold 2-fold
Icosahedral Symmetry Axes
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Icosahedral Symmetry
Each triangle is divided into 3 asymmetric unitsrelated by 3-fold axis.
5
32
T=1, 60 proteins
Minimum number of protein subunits that can form a virusshell with icosahedral symmetry is therefore equal to 60.
>> Since there are 20 faces and each face has three subunitsthe total number of subunits is 3 x 20 = 60
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Triangulation numbers, TThere are constraints preserving specificity of interactionswithin an icosahedron
-Caspar and Klug (1962)Showed that only certain multiples (1,3,4,7) of 60 subunits are likelyto occur
The more subunits used to build the virus the larger the volume itencloses
T= h2+hk+k2
where h and k are any integers
Satellite viruses, STNV are T=1Bromo viruses, T=3
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T=4T=3
180 proteins 240 proteins
Icosahedral Symmetry - Slightly More Complicated arrangements
3-fold view 2-fold view
One AU One AU
60 x T = # of subunits in a capsid. Can get up to T=217 (Iridoviridae)
Hexamer
pentamer
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Coat protein (capsid)
Capsid Proteins - Bacterial, Plant, insect and animal viruses have a similar motif - an eight-stranded antiparallel �-barrel
Inside is hydrophobicWedge-shaped arrangement seen in virus structures
Short loops
Longloops
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Examples of Viral �-barrelsSatellite tobacco necrosis virus
Polio Virus VP1
All proteins in a given virushave very similar motifs even
when there are no aminoacid similarities
Human rhinovirus 14 VP2
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Virus life cycle (structure/function)
Attachment to host cell >> Host cell receptor recognition
Protein/ligand interaction
Transfer of genetic material>> transport to nucleus
Nucleic acid and protein syntheses
Assembly
Release from host cell
Avoid immune system
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Picornaviruses
Examples common cold, polio, hepatitisSmall RNA virus (300Å diameter) Contains 4 structural proteins VP1-4VP1 -3 MW 30,000 (different aa sequences P=3)VP4 7,000 (interior)
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Surface of virus>> functioncanyon 25Å deep and 12-30Å wide
Receptor the adhesion molecule ICAM IAnti-body binding sites decoys
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Anti viral drug design
Base of VP1 hydrophobic pocket
WIN compounds bind deep inthe �-barrel motif.
Prevent uncoating
>> spin off vaccine stability
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Virus Structure - Exceptions to the �-barrel motif
Bacteriophage MS2 ssRNA genome
5-stranded anti-parallelsheet, small hairpinand two �-helices.
Dimer is the basic building block of the capsid - 10 �-strands withinterchanged �-helices
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Virus Structure - Exceptions to the �-barrel motif
Alphaviruses
Example Sinbis virusenveloped RNA genome
cause encephalitis
T=4 capsid
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Virus Structure - Other arrangements, e.g. Retroviruses
Cryo-Electron Micrograph
HIV-1 Envelope
Core
Nucleocapsid
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CPV
AAV5
AMDV
B19
ParvoviridaeFamily Portrait
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AAV5
2-fold 3-fold 5-fold
Gene therapyFuture: Gene therapy …...