Implication for alphavirus host-cell entry and assembly indicated by a 3.5Å resolution cryo-EM structure.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30552337.
- Also identified by DOI 10.1038/s41467-018-07704-x and PMC identifier 6294011.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Alphaviruses are enveloped RNA viruses that contain several human pathogens. Due to intrinsic heterogeneity of alphavirus particles, a high resolution structure of the virion is currently lacking. Here we provide a 3.5 Å cryo-EM structure of Sindbis virus, using block based reconstruction method that overcomes the heterogeneity problem. Our structural analysis identifies a number of conserved residues that play pivotal roles in the virus life cycle. We identify a hydrophobic pocket in the subdomain D of E2 protein that is stabilized by an unknown pocket factor near the viral membrane. Residues in the pocket are conserved in different alphaviruses. The pocket strengthens the interactions of the E1/E2 heterodimer and may facilitate virus assembly. Our study provides structural insights into alphaviruses that may inform the design of drugs and vaccines.
Medical subject headings
- Alphavirus
- Cryoelectron Microscopy
- Protein Interaction Domains and Motifs
- Virus Assembly
- Virus Internalization