7ASL

HIV-1 Gag immature lattice. GagSP1T8I

Summary for 7ASL

• Entry DOI: 10.2210/pdb7asl/pdb
• EMDB information: 11894 11897
• Descriptor: Gag protein (1 entity in total)
• Functional Keywords: hiv, gag, immature lattice, ca-sp1, t8i, viral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 18
• Total formula weight: 467005.79

Authors

Mendonca, L.,Zhang, P. (deposition date: 2020-10-27, release date: 2021-06-23, Last modification date: 2024-10-23)

Primary citation

Mendonca, L.,Sun, D.,Ning, J.,Liu, J.,Kotecha, A.,Olek, M.,Frosio, T.,Fu, X.,Himes, B.A.,Kleinpeter, A.B.,Freed, E.O.,Zhou, J.,Aiken, C.,Zhang, P.
CryoET structures of immature HIV Gag reveal six-helix bundle.
Commun Biol, 4:481-481, 2021

PubMed Abstract: 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 Å and 4.5 Å 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.

PubMed: 33863979
DOI: 10.1038/s42003-021-01999-1

Experimental method

ELECTRON MICROSCOPY (4.5 Å)