title: Structural basis for membrane anchoring of HIV-1 envelope spike.
abstract: HIV-1 envelope spike (Env) is a type I membrane protein that mediates viral entry. We used nuclear magnetic resonance to determine an atomic structure of the transmembrane (TM) domain of HIV-1 Env reconstituted in bicelles that mimic a lipid bilayer. The TM forms a well-ordered trimer that protects a conserved membrane-embedded arginine. An amino-terminal coiled-coil and a carboxyl-terminal hydrophilic core stabilize the trimer. Individual mutations of conserved residues did not disrupt the TM trimer and minimally affected membrane fusion and infectivity. Major changes in the hydrophilic core, however, altered the antibody sensitivity of Env. These results show how a TM domain anchors, stabilizes, and modulates a viral envelope spike and suggest that its influence on Env conformation is an important consideration for HIV-1 immunogen design.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115.|Virology Program, Harvard Medical School, 260 Longwood Avenue, Boston, MA 02115.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Dev
authors.affiliation: Division of Molecular Medicine, Boston Children's Hospital, 3 Blackfan Street, Boston, MA 02115.
authors.forename: Donghyun
authors.initials: D
authors.lastname: Park
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Division of Molecular Medicine, Boston Children's Hospital, 3 Blackfan Street, Boston, MA 02115.|Department of Pediatrics, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Molecular Medicine, Boston Children's Hospital, 3 Blackfan Street, Boston, MA 02115.|Department of Pediatrics, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115.
authors.forename: Heather Jiwon
authors.initials: HJ
authors.lastname: Ha
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.
authors.forename: Fadi
authors.initials: F
authors.lastname: Ghantous
authors.affiliation: Virology Program, Harvard Medical School, 260 Longwood Avenue, Boston, MA 02115.
authors.forename: Tobias
authors.initials: T
authors.lastname: Herrmann
authors.affiliation: Division of Molecular Medicine, Boston Children's Hospital, 3 Blackfan Street, Boston, MA 02115.
authors.forename: Weiting
authors.initials: W
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Division of Molecular Medicine, Boston Children's Hospital, 3 Blackfan Street, Boston, MA 02115.|Department of Pediatrics, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115.
authors.forename: Gary
authors.initials: G
authors.lastname: Frey
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Division of Molecular Medicine, Boston Children's Hospital, 3 Blackfan Street, Boston, MA 02115.|Department of Pediatrics, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115.|State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: James J
authors.initials: JJ
authors.lastname: Chou
mesh_terms: D001120:Arginine / Q000737:chemistry / Q000235:genetics; D015483:HIV Antibodies / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D008051:Lipid Bilayers / Q000737:chemistry; D008561:Membrane Fusion; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D055503:Protein Multimerization; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D053586:Virus Internalization
chemical_list: D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D008051:Lipid Bilayers; D001120:Arginine