2LK9

Structure of BST-2/Tetherin Transmembrane Domain

2LK9 の概要

• エントリーDOI: 10.2210/pdb2lk9/pdb
• NMR情報: BMRB: 17985
• 分子名称: Bone marrow stromal antigen 2 (1 entity in total)
• 機能のキーワード: membrane, micelle, antiviral protein-immune system complex, antiviral protein/immune system
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Golgi apparatus, trans-Golgi network: Q10589
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3920.19

構造登録者

Skasko, M.,Wang, Y.,Tian, Y.,Tokarev, A.,Munguia, J.,Ruiz, A.,Stephens, E.,Opella, S.,Guatelli, J. (登録日: 2011-10-07, 公開日: 2011-11-09, 最終更新日: 2024-05-15)

主引用文献

Skasko, M.,Wang, Y.,Tian, Y.,Tokarev, A.,Munguia, J.,Ruiz, A.,Stephens, E.B.,Opella, S.J.,Guatelli, J.
HIV-1 Vpu Protein Antagonizes Innate Restriction Factor BST-2 via Lipid-embedded Helix-Helix Interactions.
J.Biol.Chem., 287:58-67, 2012

PubMed Abstract: 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 α-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.

PubMed: 22072710
DOI: 10.1074/jbc.M111.296772

実験手法

SOLUTION NMR