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2lk9

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2lk9, 1 NMR models ()
Gene: BST2 (Homo sapiens)


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Structure of BST-2/Tetherin Transmembrane Domain

Publication Abstract from PubMed

The Vpu protein of HIV-1 antagonizes BST-2 (tetherin), a broad spectrum effector of the innate immune response to viral infection, by an intermolecular interaction that maps genetically to the alpha-helical transmembrane domains (TMDs) of each protein. Here we utilize NMR spectroscopy to describe key features of the helix-helix pairing that underlies this interaction. The antagonism of BST-2 involves a sequence of three alanines and a tryptophan spaced at four residue intervals within the Vpu TMD helix. Responsiveness to Vpu involves bulky hydrophobic residues in the C-terminal region of the BST-2 TMD helix that likely fit between the alanines on the interactive face of Vpu. These aspects of Vpu and BST-2 form an anti-parallel, lipid-embedded helix-helix interface. Changes in human BST-2 that mimic sequences found in nonhuman primate orthologs unresponsive to Vpu change the tilt angle of the TMD in the lipid bilayer without abrogating its intrinsic ability to interact with Vpu. These data explain the mechanism by which HIV-1 evades a key aspect of innate immunity and the species specificity of Vpu using an anti-parallel helix-helix packing model.

HIV-1 Vpu Protein Antagonizes Innate Restriction Factor BST-2 via Lipid-embedded Helix-Helix Interactions., Skasko M, Wang Y, Tian Y, Tokarev A, Munguia J, Ruiz A, Stephens EB, Opella SJ, Guatelli J, J Biol Chem. 2012 Jan 2;287(1):58-67. Epub 2011 Nov 9. PMID:22072710

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2lk9 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

  • Skasko M, Wang Y, Tian Y, Tokarev A, Munguia J, Ruiz A, Stephens EB, Opella SJ, Guatelli J. HIV-1 Vpu Protein Antagonizes Innate Restriction Factor BST-2 via Lipid-embedded Helix-Helix Interactions. J Biol Chem. 2012 Jan 2;287(1):58-67. Epub 2011 Nov 9. PMID:22072710 doi:10.1074/jbc.M111.296772

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