Virus Structure Flashcards
What is the structure of a viral particle
Many viruses are found to have icosahedral symmetry
- solid 20 triangular faces
- 12 vertices
- related by 2,3 and 5 fold axis of rotational symmetry
Many enveloped animal RNA viruses have helical nucleocapsids
What are the different methods to study virus structure
- Electron microscopy
- Cryo-electron Microscopy
- X-ray crystallography
- Cryo-electron tomography
- AI appraoches: AlphaFold
What does the Electron Microscopy show
- Particles that are negatively stained
- Main features identifiable are morphological units
- Resolution: 50-70 A
What does Cryo-electron Microscopy
- Virus must symmetrical and at high concentration
- Samples are rapidly frozen in a hydrated state
- Preserves the native structure
- Shows contrast in the virus structure itself
- 3D image reconstruction possible resolution can show less than 2A
What does X-ray crystallography show
This is only applicable to components of larger viruses
In the case of smaller viruses, viruses must form crystals first
What does Cyro-electron tomography show
- It combines both cryo-preservation with electron tomography
- It is suitable for visualising large biological structures that lack any obvious symmetry up to the level of cellular assemblies
How does AI (like AlphaFold) help with studying virus structures.
More than 180,000 experimentally determined protein structures
UniProt protein databases contains 230 million confirmed or predicted proteins
The AlphaFold databases now contains a structural prediction for over 200 million proteins
What does AI use to predict these structures
Refines cryo-EM structures and combines particle and protein structures
Predict viral protein structure based only on the nucleotide sequence
Determines evolutionary relationships between viruses based on the structural proteins on the receptor and antibody binding
What is the Flavivirus Envelope formation
- prM and E inserted into the ER lumen and during translation
- Signalase cleavage, folding, glycosylation (ER lumen)
- The nucleocapsid buds into the ER lumen
What does the prM protein do
It protects the E protein from premature fusion
What is the Flavivirus E protein structure
- It is a 3 domain protein
- Forms a head to tail dimer at neutral pH
- Lies parallel to the virion membrane
- Domain III receptor binding
- Domain II fusion domain - contains a fusion peptide
What is the structure of immature Flavivirus Particles
- Particles have 60 irregular trimeric E protein spikes
- Fusion peptide projected outwards
- The pr protein caps each of the spikes protecting the fusion peptide
How do you design a vaccine based on structure
- Mapping of antibody binding sites
- An available structure can be used to map neutralising and non-neutralising antibodies
- Antibody escape mutants and mutated recombinant E protein subunits can be used for this purpose in combination with antibody binding studies
What are antibody escape mutants
These are virus variants that have developed mutations allowing them to evade binding by certain antibodies. By studying these mutants, researchers can determine which regions of the viral protein are essential for antibody recognition
What is the mutated recombinant E protein
The E (Envelope) protein is often a key target for vaccines, especially for viruses like Flaviviruses. Scientists can create modified versions of the E protein with specific mutations to see how these changes affect antibody binding.
