5WTF

Cryo-EM structure for Hepatitis A virus empty particle

Summary for 5WTF

• Entry DOI: 10.2210/pdb5wtf/pdb
• Related: 5WTE 5WTH
• EMDB information: 6686 6687 6688
• Descriptor: VP1, VP0, VP3 (3 entities in total)
• Functional Keywords: hav, neutralizing mechanism, receptor recognition, viral entry, virus
• Biological source: Hepatitis A virus; More
• Total number of polymer chains: 3
• Total formula weight: 75762.91

Authors

Wang, X.,Zhu, L.,Dang, M.,Hu, Z.,Gao, Q.,Yuan, S.,Sun, Y.,Zhang, B.,Ren, J.,Walter, T.S.,Wang, J.,Fry, E.E.,Stuart, D.I.,Rao, Z. (deposition date: 2016-12-11, release date: 2017-01-25, Last modification date: 2024-03-27)

Primary citation

Wang, X.,Zhu, L.,Dang, M.,Hu, Z.,Gao, Q.,Yuan, S.,Sun, Y.,Zhang, B.,Ren, J.,Kotecha, A.,Walter, T.S.,Wang, J.,Fry, E.E.,Stuart, D.I.,Rao, Z.
Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site
Proc. Natl. Acad. Sci. U.S.A., 114:770-775, 2017

PubMed Abstract: Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention.

PubMed: 28074040
DOI: 10.1073/pnas.1616502114

Experimental method

ELECTRON MICROSCOPY (3.9 Å)