title: Crystal structure of a soluble cleaved HIV-1 envelope trimer.
abstract: HIV-1 entry into CD4(+) target cells is mediated by cleaved envelope glycoprotein (Env) trimers that have been challenging to characterize structurally. Here, we describe the crystal structure at 4.7 angstroms of a soluble, cleaved Env trimer that is stabilized and antigenically near-native (termed the BG505 SOSIP.664 gp140 trimer) in complex with a potent broadly neutralizing antibody, PGT122. The structure shows a prefusion state of gp41, the interaction between the component gp120 and gp41 subunits, and how a close association between the gp120 V1/V2/V3 loops stabilizes the trimer apex around the threefold axis. The complete epitope of PGT122 on the trimer involves gp120 V1, V3, and several surrounding glycans. This trimer structure advances our understanding of how Env functions and is presented to the immune system, and provides a blueprint for structure-based vaccine design.
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Julien
authors.forename: Albert
authors.initials: A
authors.lastname: Cupo
authors.forename: Devin
authors.initials: D
authors.lastname: Sok
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Stanfield
authors.forename: Dmitry
authors.initials: D
authors.lastname: Lyumkis
authors.forename: Marc C
authors.initials: MC
authors.lastname: Deller
authors.forename: Per-Johan
authors.initials: PJ
authors.lastname: Klasse
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
authors.forename: John P
authors.initials: JP
authors.lastname: Moore
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Ward
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
mesh_terms: D057134:Antibodies, Neutralizing / Q000737:chemistry; D000914:Antibodies, Viral / Q000737:chemistry; D018360:Crystallography, X-Ray; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology; D006801:Humans; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D012995:Solubility; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; C514787:gp41 protein, Human immunodeficiency virus 1