Lecture 3 - Viral Architecture Flashcards
What is the virual struture consist of?
Nucleic acid (DNA or RNA) Outer shell (capsid) Nucleocapsid: nucleic acid genome packaged within the capsid \+/- Envelope
What is the function of the Viral Capsid?
Describe the Capsid Design
What are viral capsids?
Capsomers?
- Proteins associate into identical structural units called capsomers or capsomeres.
- Capsomers are arranged symmetrically around viral genome.
- Can consist of one type of protein or several different protein subunits.
What is involved in the self- assembly of a virus?
Economy and efficiency
Construction and rapid assembly of “basic units”
Sub-assembled structures form and break apart on route to the most stable structure
12 solid yellow pieces represent viral subunits
Magnets represent attractive forces between subunits.
Strength of shaking represents temperature of microenvironment
Describe Virus-like particles
Self-assembly sometimes results in particles empty of genetic material
Not infectious, but immunogenic
Vaccine approach; safer alternative to attenuated viruses
Delivery system for genes or other therapeutics
Describe Helical Capsids
- Simplest way to arrange multiple, identical protein subunits is to use rotational symmetry
- Arrange the irregularly shaped proteins around the circumference of a circle to form a disc
- Central cavity
- Length of capsid related to length of nucleic acid within.
- ssRNA, ssDNA in some cases
- Diameter dependent on the size and arrangement of capsomers
Describe Icosahedral shape
Most animal viruses are icosahedral or near-spherical with icosahedral symmetry
Regular polyhedron with:
20 identical equilateral triangular faces
30 edges
2 vertices
optimal way of forming a closed shell from identical protein sub-units (capsomeres)
minimum of 3 subunits per face(60 total)
Most virions, due to their size, have more than 60 subunits
What is a 5-3-2 axis symmetry?
12 five-fold rotation axes
20 three-fold rotational axes
30 two-fold rotational axes
Why do larger viruses assemble in complex packages?
True icosaherdron consists of only 20 facets/subunits
Difficult for >60 subunits to be arranged in an equivalent fashion
Casper and Klug (1962)
Quasi-equivalent bonding
Triangulation number: # of subunits per facet or simply 60 x N
What is the triangulation number (T-number)?
Number used to describe the relation between the # of:
Pentamers= capsomers at the apices surrounded by 5 other capsomers
Hexamers= capsomers on the triangular faces surrounded by 6 other capsomers
12 subunits x 20 = 240
What is Quasi-equivalent Bonding?
- Attainment of maximum stability is overriding factor determining final structure of a virus particle
- More economical to use 180 identical subunits to build a capsid than 60 copies each of three different proteins
- Subunits will not all be in identical positions
- Distinct binding interactions with nearest neighbors
- Requirement for nearly-equivalent bonding arrangements
- “any small variation in regular internal bonding pattern leading to a more stable structure”
Each comma is a subunit 180 subunits (T=3) Head-to-head, neck-to-neck, tail-to-tail interactions 60 tail-to-tail interactions in clusters of 5 (“A”) 120 tail-to-tail interactions in clusters of 6 (“B” and “C”) Subunits do not need to bind all three places with each other
Why Subunit Construction? What is involved?
- Necessity: small genome; viruses are 50-90% protein
- Self-assembly: free energy minimum
- Fidelity: smaller protein means less chance of error occurring
- Economy: correct structure can be formed with minimal waste; only small incorrect subunits need to be discarded
- Complexity: larger the number of the subunits, the more stable the virus becomes; larger particle means a bigger genome
What kind of influence does the nucleic acid have on the structure?
- ssRNA viruses often possess helical capsid structure
- Cylinder container allows for direct contact between (-) charged nucleic acid and (+) charged protein subunits
- Almost all dsDNA viruses have icosahedral symmetry
- Circular DNA, highly coiled
- Compact globular structure easily contained within a spherical capsid
The structure of a virus whether it is naked or enveloped