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TitleThe membrane-proximal external region of human immunodeficiency virus (HIV-1) envelope glycoprotein trimers in A18-lipid nanodiscs.
Journal, issue, pagesCommun Biol, Vol. 8, Issue 1, Page 442, Year 2025
Publish dateMar 15, 2025
AuthorsYi Qi / Shijian Zhang / Kunyu Wang / Haitao Ding / Zhiqing Zhang / Saumya Anang / Hanh T Nguyen / John C Kappes / Joseph Sodroski / Youdong Mao /
PubMed AbstractDuring human immunodeficiency virus (HIV-1) entry, the metastable pretriggered envelope glycoprotein (Env) trimer ((gp120/gp41)) opens asymmetrically. We present cryo-EM structures of cleaved ...During human immunodeficiency virus (HIV-1) entry, the metastable pretriggered envelope glycoprotein (Env) trimer ((gp120/gp41)) opens asymmetrically. We present cryo-EM structures of cleaved asymmetric Env trimers in amphipol-lipid nanodiscs. The gp41 membrane-proximal external region (MPER) could be traced in Env protomers that remained close to the nanodisc despite Env tilting. The MPER interacts with the gp120 C-termini and gp41 α9 helices at the base of the Env trimer. MPER conformation is coupled with the tilt angles of the α9 helices, the helicity of the gp41 heptad repeat (HR1) regions, and the opening angles between the protomers of the asymmetric trimers. Our structural models explain the stabilizing effects of MPER integrity and Env proteolytic maturation on the pretriggered Env conformation. Superimposed on the asymmetry of the Env protomers, variation in the glycans at the trimer apex creates substantial structural heterogeneity in the V2 quaternary epitopes of difficult-to-elicit broadly neutralizing antibodies.
External linksCommun Biol / PubMed:40089599 / PubMed Central
MethodsEM (single particle)
Resolution3.4 - 3.5 Å
Structure data

61553

9jkf

EMDB-61553, PDB-9jkf:
Asymmetric structure of cleaved HIV-1 Tri FPPR envelope glycoprotein trimer in amphipol-lipid nanodiscs (Tri FPPR.1)
Method: EM (single particle) / Resolution: 3.4 Å

61554

9jkg

EMDB-61554, PDB-9jkg:
Asymmetric structure of cleaved HIV-1 Tri FPPR envelope glycoprotein trimer in amphipol-lipid nanodiscs (Tri FPPR.2)
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

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

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

Source
  • simian-human immunodeficiency virus
KeywordsVIRAL PROTEIN / viral entry

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