Structural basis of HIV-1 tethering to membranes by the BST-2/tetherin ectodomain.
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.
Hinz
Andreas
A
Unit of Virus Host Cell Interactions (UVHCI) UMI 3265 Université Joseph Fourier-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France.
Miguet
Nolwenn
N
Unit of Virus Host Cell Interactions (UVHCI) UMI 3265 Université Joseph Fourier-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France.
Natrajan
Ganesh
G
Unit of Virus Host Cell Interactions (UVHCI) UMI 3265 Université Joseph Fourier-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France.
Usami
Yoshiko
Y
Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Yamanaka
Hikaru
H
Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Renesto
Patricia
P
Unit of Virus Host Cell Interactions (UVHCI) UMI 3265 Université Joseph Fourier-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France.
Hartlieb
Bettina
B
Unit of Virus Host Cell Interactions (UVHCI) UMI 3265 Université Joseph Fourier-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France.
McCarthy
Andrew A
AA
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.
Simorre
Jean-Pierre
JP
Institut de Biologie Structurale Jean-Pierre Ebel, UMR 5075 CEA-CNRS-UJF, 41 rue Jules Horowitz, 38027 Grenoble Cedex 01, France.
Göttlinger
Heinrich
H
Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Weissenhorn
Winfried
W
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.
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
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2
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