Module 3: Structure of Viruses

Virology

range in size

20 to 400 nm in diameter

capsid

protien coat covering nucleic acid genome

spikes

protien or glycoprotien structures on the surface of virus particles invloved in receptor binding on host cells

subunit

single folded polypeptide chain

structural unit

unit from which capsids or nucleocapsids are built

envelope

host cell derived lipid bilayer

Function of virons

• protection of genome

• delivery of genome

• package critical viral enzymes into target cells

• interactions with cell components to ensure infectious cycle

genome packaging challenges

• extreme electrostatic repulsion

• high internal pressure

• steric confinement

• ordered condensation

virus particles are _______

metastable

metastable

flip between a stable and unstable state

stable - must protect the genome

unstable - must come apart on infection to uncoat

how to achieve metastability?

• spring loaded energy

• reversible bonds

• kinetic trapping

• environmental cues

tools used for viral structural biology

• electron microscopy

• x-ray crystallography

• cryo-election microscopy (cryoEM) & cryoelectron tomography

parameters for helical symmetry

• identical inter-subunit contacts

• pitch of helix (P) - P= μ x p (μ is subunits per turn and p is axial rise per subunit)

• open-ended architectyre

• RNA co-assembly

Identical inter-subunit contacts

coat protein molecules engage in identical interactions with one another

Pitch of helix (P)

defined as P = μ × p, where μ is subunits per turn and p is axial rise per subunit

Open-ended architecture

unlike icosahedral capsids, they can adapt length to accommodate variable genome sizes

RNA co-assembly

single-stranded viral RNA winds inside a helical groove, stabilizing the tube

Genome packaging challenges

• extreme electrostatic repulsion

• high internal pressure

• steric confinment

• ordered condensation

Three virus particle shapes

• helical

• icosahedral

• complex

Genetic Economy Principle

• viral genomes dont have coding capacity for large single protien coats

• mutimeric repeat strategy - multiple copies of identical small protien subunits

• maximized volume - repeat identical unite —> large internal volumetric storage & minimal coding DNA

• error reduction

• symmetry requirement

Symmetry rules

Rule 1 - each subunit has identical bonding contacts with this neighbors

Rule 2 - these bonding contacts are usually non-covalent (reversible & error free)

Why are animal viruses with helical symmetry always enveloped?

It is for survival. Non-enveloped helical capsids would be too unstable to survuve the physical and chemical attachs in an animal host cells

The envelope acts as a protective flexible cushion that stabilizes the long helical capsid.

How can you make a round capsid from protiens with irregular shapes?

• Clue 1 - all round capsids have a precise number of protiens - multiples of 60 are common (60, 180, 240, 960)

• Clue 2 - Spherical viruses come in many sizes, but capsie protiens are 20 - 60 kDa average.

W&C called these icosahedral symmetry

Icosahedral symmetry parameters

• closed spherical shell - optimal geometric design for forming a closed shell from subunit repeats

• faces - 20 equilateral triangular faces and 12 vertices

• three rotational axes - 5 fold (vertices), 3 fold (face centers), and 2 fold (edge centers) axes of symmetry

• subunit minimum - n=60 identical subunits required for a closed icosahedron

• maximized internal volume

simple icosahedral capsids (T=1)

• made of 60 identical protien subunits arranged as 12 pentamers (n=5 subunits)

• interactions of all molecules are identical (head to head, tail to tail)