title: Structural basis of HIV-1 tethering to membranes by the BST-2/tetherin ectodomain.
abstract: The restriction factor BST-2/tetherin contains two membrane anchors employed to retain some enveloped viruses, including HIV-1 tethered to the plasma membrane in the absence of virus-encoded antagonists. The 2.77 A crystal structure of the BST-2/tetherin extracellular core presented here reveals a parallel 90 A long disulfide-linked coiled-coil domain, while the complete extracellular domain forms an extended 170 A long rod-like structure based on small-angle X-ray scattering data. Mutagenesis analyses indicate that both the coiled coil and the N-terminal region are required for retention of HIV-1, suggesting that the elongated structure can function as a molecular ruler to bridge long distances. The structure reveals substantial irregularities and instabilities throughout the coiled coil, which contribute to its low stability in the absence of disulfide bonds. We propose that the irregular coiled coil provides conformational flexibility, ensuring that BST-2/tetherin anchoring both in the plasma membrane and in the newly formed virus membrane is maintained during virus budding.
authors.affiliation: Unit of Virus Host Cell Interactions (UVHCI) UMI 3265 Université Joseph Fourier-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hinz
authors.affiliation: Unit of Virus Host Cell Interactions (UVHCI) UMI 3265 Université Joseph Fourier-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Miguet
authors.affiliation: Unit of Virus Host Cell Interactions (UVHCI) UMI 3265 Université Joseph Fourier-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Natrajan
authors.affiliation: Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Usami
authors.affiliation: Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: Unit of Virus Host Cell Interactions (UVHCI) UMI 3265 Université Joseph Fourier-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Renesto
authors.affiliation: Unit of Virus Host Cell Interactions (UVHCI) UMI 3265 Université Joseph Fourier-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France.
authors.forename: Bettina
authors.initials: B
authors.lastname: Hartlieb
authors.affiliation: Unit of Virus Host Cell Interactions (UVHCI) UMI 3265 Université Joseph Fourier-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France; EMBL, 6 rue Jules Horowitz, 38042 Grenoble, France.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: McCarthy
authors.affiliation: Institut de Biologie Structurale Jean-Pierre Ebel, UMR 5075 CEA-CNRS-UJF, 41 rue Jules Horowitz, 38027 Grenoble Cedex 01, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Simorre
authors.affiliation: Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Göttlinger
authors.affiliation: Unit of Virus Host Cell Interactions (UVHCI) UMI 3265 Université Joseph Fourier-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France. Electronic address: weissenhorn@embl.fr.
authors.forename: Winfried
authors.initials: W
authors.lastname: Weissenhorn
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000821:virology*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D058851:GPI-Linked Proteins; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D057074:Virus Release; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2
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