6VWS

Hexamer of Helical HIV capsid by RASTR method

Summary for 6VWS

• Entry DOI: 10.2210/pdb6vws/pdb
• EMDB information: 21423
• Descriptor: HIV capsid protein (1 entity in total)
• Functional Keywords: helical reconstruction, gs-6207 hexamer hiv, viral protein, rastr
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 6
• Total formula weight: 147679.04

Authors

Zhao, H.,Iqbal, N.,Asturias, F.,Kvaratskhelia, M.,Vanblerkom, P. (deposition date: 2020-02-20, release date: 2020-10-21, Last modification date: 2024-03-06)

Primary citation

Bester, S.M.,Wei, G.,Zhao, H.,Adu-Ampratwum, D.,Iqbal, N.,Courouble, V.V.,Francis, A.C.,Annamalai, A.S.,Singh, P.K.,Shkriabai, N.,Van Blerkom, P.,Morrison, J.,Poeschla, E.M.,Engelman, A.N.,Melikyan, G.B.,Griffin, P.R.,Fuchs, J.R.,Asturias, F.J.,Kvaratskhelia, M.
Structural and mechanistic bases for a potent HIV-1 capsid inhibitor.
Science, 370:360-364, 2020

PubMed Abstract: The potent HIV-1 capsid inhibitor GS-6207 is an investigational principal component of long-acting antiretroviral therapy. We found that GS-6207 inhibits HIV-1 by stabilizing and thereby preventing functional disassembly of the capsid shell in infected cells. X-ray crystallography, cryo-electron microscopy, and hydrogen-deuterium exchange experiments revealed that GS-6207 tightly binds two adjoining capsid subunits and promotes distal intra- and inter-hexamer interactions that stabilize the curved capsid lattice. In addition, GS-6207 interferes with capsid binding to the cellular HIV-1 cofactors Nup153 and CPSF6 that mediate viral nuclear import and direct integration into gene-rich regions of chromatin. These findings elucidate structural insights into the multimodal, potent antiviral activity of GS-6207 and provide a means for rationally developing second-generation therapies.

PubMed: 33060363
DOI: 10.1126/science.abb4808

Experimental method

ELECTRON MICROSCOPY (6.08 Å)