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Publication Abstract from PubMed

Gag is the HIV structural precursor protein which is cleaved by viral protease to produce mature infectious viruses. Gag is a polyprotein composed of MA (matrix), CA (capsid), SP1, NC (nucleocapsid), SP2 and p6 domains. SP1, together with the last eight residues of CA, have been hypothesized to form a six-helix bundle responsible for the higher-order multimerization of Gag necessary for HIV particle assembly. However, the structure of the complete six-helix bundle has been elusive. Here, we determined the structures of both Gag in vitro assemblies and Gag viral-like particles (VLPs) to 4.2 A and 4.5 A resolutions using cryo-electron tomography and subtomogram averaging by emClarity. A single amino acid mutation (T8I) in SP1 stabilizes the six-helix bundle, allowing to discern the entire CA-SP1 helix connecting to the NC domain. These structures provide a blueprint for future development of small molecule inhibitors that can lock SP1 in a stable helical conformation, interfere with virus maturation, and thus block HIV-1 infection.

CryoET structures of immature HIV Gag reveal six-helix bundle.,Mendonca L, Sun D, Ning J, Liu J, Kotecha A, Olek M, Frosio T, Fu X, Himes BA, Kleinpeter AB, Freed EO, Zhou J, Aiken C, Zhang P Commun Biol. 2021 Apr 16;4(1):481. doi: 10.1038/s42003-021-01999-1. PMID:33863979^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.