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TitleAsymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody.
Journal, issue, pagesNat Struct Mol Biol, Vol. 26, Issue 12, Page 1167-1175, Year 2019
Publish dateDec 2, 2019
AuthorsZhi Yang / Haoqing Wang / Albert Z Liu / Harry B Gristick / Pamela J Bjorkman /
PubMed AbstractThe human immunodeficiency virus (HIV-1) envelope (Env) glycoprotein, a (gp120-gp41) trimer, mediates fusion of viral and host cell membranes after gp120 binding to host receptor CD4. Receptor ...The human immunodeficiency virus (HIV-1) envelope (Env) glycoprotein, a (gp120-gp41) trimer, mediates fusion of viral and host cell membranes after gp120 binding to host receptor CD4. Receptor binding triggers conformational changes allowing coreceptor (CCR5) recognition through CCR5's tyrosine-sulfated amino (N) terminus, release of the gp41 fusion peptide and fusion. We present 3.3 Å and 3.5 Å cryo-EM structures of E51, a tyrosine-sulfated coreceptor-mimicking antibody, complexed with a CD4-bound open HIV-1 native-like Env trimer. Two classes of asymmetric Env interact with E51, revealing tyrosine-sulfated interactions with gp120 mimicking CCR5 interactions, and two conformations of gp120-gp41 protomers (A and B protomers in AAB and ABB trimers) that differ in their degree of CD4-induced trimer opening and induction of changes to the fusion peptide. By integrating the new structural information with previous closed and open envelope trimer structures, we modeled the order of conformational changes on the path to coreceptor binding site exposure and subsequent viral-host cell membrane fusion.
External linksNat Struct Mol Biol / PubMed:31792452 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 3.5 Å
Structure data

20605

6u0l

EMDB-20605, PDB-6u0l:
Asymmetrically open conformational state (Class I) of HIV-1 Env trimer BG505 SOSIP.664 in complex with sCD4 and E51 Fab
Method: EM (single particle) / Resolution: 3.3 Å

20608

6u0n

EMDB-20608, PDB-6u0n:
Asymmetrically open conformational state (Class II) of HIV-1 Env trimer BG505 SOSIP.664 in complex with sCD4 and E51 Fab
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

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

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / BG505 SOSIP.664 / E51 / sCD4 / Env / Env open conformation / asymmetrically open Env

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