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TitleAn Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity.
Journal, issue, pagesCell Host Microbe, Vol. 25, Issue 4, Page 578-587.e5, Year 2019
Publish dateApr 10, 2019
AuthorsNirmin Alsahafi / Nordine Bakouche / Mohsen Kazemi / Jonathan Richard / Shilei Ding / Sudipta Bhattacharyya / Durba Das / Sai Priya Anand / Jérémie Prévost / William D Tolbert / Hong Lu / Halima Medjahed / Gabrielle Gendron-Lepage / Gloria Gabrielle Ortega Delgado / Sharon Kirk / Bruno Melillo / Walther Mothes / Joseph Sodroski / Amos B Smith / Daniel E Kaufmann / Xueling Wu / Marzena Pazgier / Isabelle Rouiller / Andrés Finzi / James B Munro /
PubMed AbstractThe HIV-1 envelope glycoprotein (Env) (gp120-gp41) is the target for neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC). HIV-1 Env is flexible, sampling different ...The HIV-1 envelope glycoprotein (Env) (gp120-gp41) is the target for neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC). HIV-1 Env is flexible, sampling different conformational states. Before engaging CD4, Env adopts a closed conformation (State 1) that is largely antibody resistant. CD4 binding induces an intermediate state (State 2), followed by an open conformation (State 3) that is susceptible to engagement by antibodies that recognize otherwise occluded epitopes. We investigate conformational changes in Env that induce ADCC in the presence of a small-molecule CD4-mimetic compound (CD4mc). We uncover an asymmetric Env conformation (State 2A) recognized by antibodies targeting the conserved gp120 inner domain and mediating ADCC. Sera from HIV+ individuals contain these antibodies, which can stabilize Env State 2A in combination with CD4mc. Additionally, triggering State 2A on HIV-infected primary CD4 T cells exposes epitopes that induce ADCC. Strategies that induce this Env conformation may represent approaches to fight HIV-1 infection.
External linksCell Host Microbe / PubMed:30974085 / PubMed Central
MethodsEM (single particle)
Resolution13.08 Å
Structure data

EMDB-0466:
HIV-1 Env State 2A
Method: EM (single particle) / Resolution: 13.08 Å

Source
  • Human immunodeficiency virus 1

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