Structure of HIV-1 gp41 with its membrane anchors targeted by neutralizing antibodies

eLife

Winfried Weissenhorn¹  François L Dehez²  Alexandra Trkola³  Nikolas Friedrich³  Jose L Nieva⁴  Johana Torralba⁴  Christophe J Chipot⁵  Christophe Caillat⁶  Delphine Guilligay⁶ 

[1] Department of Physics, University of Illinois at Urbana-Champaign, Urbana, United States;Laboratoire International Associé, CNRS and University of Illinois at Urbana-Champaign, Vandoeuvre-lès-Nancy, France;Institute of Medical Virology, University of Zurich, Zurich, Switzerland;Instituto Biofisika (CSIC, UPV/EHU) and Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), Bilbao, Spain;Laboratoire de Physique et Chimie Théoriques (LPCT), University of Lorraine, Vandoeuvre-lès-Nancy, France;Univ. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), Grenoble, France;

关键词: HIV-1;    gp41;    membrane fusion;    LN01;    4E10;    2H10;   

DOI  :  10.7554/eLife.65005

来源: DOAJ

【 摘 要 】

The HIV-1 gp120/gp41 trimer undergoes a series of conformational changes in order to catalyze gp41-induced fusion of viral and cellular membranes. Here, we present the crystal structure of gp41 locked in a fusion intermediate state by an MPER-specific neutralizing antibody. The structure illustrates the conformational plasticity of the six membrane anchors arranged asymmetrically with the fusion peptides and the transmembrane regions pointing into different directions. Hinge regions located adjacent to the fusion peptide and the transmembrane region facilitate the conformational flexibility that allows high-affinity binding of broadly neutralizing anti-MPER antibodies. Molecular dynamics simulation of the MPER Ab-stabilized gp41 conformation reveals a possible transition pathway into the final post-fusion conformation with the central fusion peptides forming a hydrophobic core with flanking transmembrane regions. This suggests that MPER-specific broadly neutralizing antibodies can block final steps of refolding of the fusion peptide and the transmembrane region, which is required for completing membrane fusion.

【 授权许可】

Unknown