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TitleCryoET structures of immature HIV Gag reveal six-helix bundle.
Journal, issue, pagesCommun Biol, Vol. 4, Issue 1, Page 481, Year 2021
Publish dateApr 16, 2021
AuthorsLuiza Mendonça / Dapeng Sun / Jiying Ning / Jiwei Liu / Abhay Kotecha / Mateusz Olek / Thomas Frosio / Xiaofeng Fu / Benjamin A Himes / Alex B Kleinpeter / Eric O Freed / Jing Zhou / Christopher Aiken / Peijun Zhang /
PubMed AbstractGag 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), ...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.
External linksCommun Biol / PubMed:33863979 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution4.2 - 15.1 Å
Structure data

11894

7ash

EMDB-11894, PDB-7ash:
HIV-1 Gag immature lattice. GagdeltaMASP1T8I
Method: EM (subtomogram averaging) / Resolution: 4.2 Å

11897

7asl

EMDB-11897, PDB-7asl:
HIV-1 Gag immature lattice. GagSP1T8I
Method: EM (subtomogram averaging) / Resolution: 4.5 Å

EMDB-11899:
HIV-1 Gag immature lattice. GagdeltaMASP1T8I with IP-6
Method: EM (subtomogram averaging) / Resolution: 4.2 Å

EMDB-12287:
HIV-1 Gag T8I NC-RNA layer
Method: EM (subtomogram averaging) / Resolution: 15.1 Å

Source
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN / HIV-1 / Gag / immature lattice / SP1 / T8I / HIV / CA-SP1

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