title: Broadly Neutralizing Antibody 8ANC195 Recognizes Closed and Open States of HIV-1 Env.
abstract: The HIV-1 envelope (Env) spike contains limited epitopes for broadly neutralizing antibodies (bNAbs); thus, most neutralizing antibodies are strain specific. The 8ANC195 epitope, defined by crystal and electron microscopy (EM) structures of bNAb 8ANC195 complexed with monomeric gp120 and trimeric Env, respectively, spans the gp120 and gp41 Env subunits. To investigate 8ANC195's gp41 epitope at higher resolution, we solved a 3.58 Å crystal structure of 8ANC195 complexed with fully glycosylated Env trimer, revealing 8ANC195 insertion into a glycan shield gap to contact gp120 and gp41 glycans and protein residues. To determine whether 8ANC195 recognizes the CD4-bound open Env conformation that leads to co-receptor binding and fusion, one of several known conformations of virion-associated Env, we solved EM structures of an Env/CD4/CD4-induced antibody/8ANC195 complex. 8ANC195 binding partially closed the CD4-bound trimer, confirming structural plasticity of Env by revealing a previously unseen conformation. 8ANC195's ability to bind different Env conformations suggests advantages for potential therapeutic applications.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Scharf
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Haoqing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Gao
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Songye
authors.initials: S
authors.lastname: Chen
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Alasdair W
authors.initials: AW
authors.lastname: McDowall
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: bjorkman@caltech.edu.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
mesh_terms: D057134:Antibodies, Neutralizing / Q000378:metabolism* / Q000648:ultrastructure; D000939:Epitopes; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D011487:Protein Conformation; D014961:X-Ray Diffraction
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G