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TitleA sequestered fusion peptide in the structure of an HIV-1 transmitted founder envelope trimer.
Journal, issue, pagesNat Commun, Vol. 10, Issue 1, Page 873, Year 2019
Publish dateFeb 20, 2019
AuthorsNeeti Ananthaswamy / Qianglin Fang / Wadad AlSalmi / Swati Jain / Zhenguo Chen / Thomas Klose / Yingyuan Sun / Yue Liu / Marthandan Mahalingam / Subhash Chand / Sodsai Tovanabutra / Merlin L Robb / Michael G Rossmann / Venigalla B Rao /
PubMed AbstractThe envelope protein of human immunodeficiency virus-1 (HIV-1) and its fusion peptide are essential for cell entry and vaccine design. Here, we describe the 3.9-Å resolution structure of an envelope ...The envelope protein of human immunodeficiency virus-1 (HIV-1) and its fusion peptide are essential for cell entry and vaccine design. Here, we describe the 3.9-Å resolution structure of an envelope protein trimer from a very early transmitted founder virus (CRF01_AE T/F100) complexed with Fab from the broadly neutralizing antibody (bNAb) 8ANC195. The overall T/F100 trimer structure is similar to other reported "closed" state prefusion trimer structures. In contrast, the fusion peptide, which is exposed to solvent in reported closed structures, is sequestered (buried) in the hydrophobic core of the T/F100 trimer. A buried conformation has previously been observed in "open" state structures formed after CD4 receptor binding. The T/F100 trimer binds poorly to bNAbs including the fusion peptide-specific bNAbs PGT151 and VRC34.01. The T/F100 structure might represent a prefusion state, intermediate between the closed and open states. These observations are relevant to mechanisms of HIV-1 transmission and vaccine design.
External linksNat Commun / PubMed:30787293 / PubMed Central
MethodsEM (single particle)
Resolution3.9 Å
Structure data

0485

6nqd

EMDB-0485, PDB-6nqd:
Cryo-EM structure of T/F100 SOSIP.664 HIV-1 Env trimer in complex with 8ANC195 Fab
Method: EM (single particle) / Resolution: 3.9 Å

Chemicals

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

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 / Env / trimer / VIRAL PROTEIN-IMMUNE SYSTEM complex

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