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TitleAsymmetric conformations of cleaved HIV-1 envelope glycoprotein trimers in styrene-maleic acid lipid nanoparticles.
Journal, issue, pagesCommun Biol, Vol. 6, Issue 1, Page 535, Year 2023
Publish dateMay 18, 2023
AuthorsKunyu Wang / Shijian Zhang / Eden P Go / Haitao Ding / Wei Li Wang / Hanh T Nguyen / John C Kappes / Heather Desaire / Joseph Sodroski / Youdong Mao /
PubMed AbstractDuring virus entry, the pretriggered human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer initially transits into a default intermediate state (DIS) that remains structurally ...During virus entry, the pretriggered human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer initially transits into a default intermediate state (DIS) that remains structurally uncharacterized. Here, we present cryo-EM structures at near-atomic resolution of two cleaved full-length HIV-1 Env trimers purified from cell membranes in styrene-maleic acid lipid nanoparticles without antibodies or receptors. The cleaved Env trimers exhibited tighter subunit packing than uncleaved trimers. Cleaved and uncleaved Env trimers assumed remarkably consistent yet distinct asymmetric conformations, with one smaller and two larger opening angles. Breaking conformational symmetry is allosterically coupled with dynamic helical transformations of the gp41 N-terminal heptad repeat (HR1) regions in two protomers and with trimer tilting in the membrane. The broken symmetry of the DIS potentially assists Env binding to two CD4 receptors-while resisting antibody binding-and promotes extension of the gp41 HR1 helical coiled-coil, which relocates the fusion peptide closer to the target cell membrane.
External linksCommun Biol / PubMed:37202420 / PubMed Central
MethodsEM (single particle)
Resolution3.8 - 5.0 Å
Structure data

28953

8fad

EMDB-28953, PDB-8fad:
Asymmetric structure of cleaved HIV-1 AD8 envelope glycoprotein trimer in styrene-maleic acid lipid nanoparticles
Method: EM (single particle) / Resolution: 4.0 Å

28954

8fae

EMDB-28954, PDB-8fae:
Asymmetric structure of cleaved HIV-1 AE2 envelope glycoprotein trimer in styrene-maleic acid lipid nanoparticles (AE2.1)
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-28955: Asymmetric structure of cleaved HIV-1 AE2 envelope glycoprotein trimer in styrene-maleic acid lipid nanoparticles (AE2.2)
Method: EM (single particle) / Resolution: 5.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-83G:
1-[(2R)-4-(benzenecarbonyl)-2-methylpiperazin-1-yl]-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethane-1,2-dione

Source
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN / HIV-1 / envelope glycoprotein

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