6OWT

Structure of SIVsmm Nef and SMM tetherin bound to the clathrin adaptor AP-2 complex

6OWT の概要

• エントリーDOI: 10.2210/pdb6owt/pdb
• EMDBエントリー: 20217
• 分子名称: AP-2 complex subunit alpha, AP-2 complex subunit beta, Adaptor protein complex AP-2, mu1, ... (5 entities in total)
• 機能のキーワード: ap, hiv, nef, trafficking, protein transport, viral restriction factor
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 267957.52

構造登録者

Buffalo, C.Z.,Ren, X.,Hurley, J.H. (登録日: 2019-05-10, 公開日: 2019-09-25, 最終更新日: 2025-05-28)

主引用文献

Buffalo, C.Z.,Sturzel, C.M.,Heusinger, E.,Kmiec, D.,Kirchhoff, F.,Hurley, J.H.,Ren, X.
Structural Basis for Tetherin Antagonism as a Barrier to Zoonotic Lentiviral Transmission.
Cell Host Microbe, 26:359-368.e8, 2019

PubMed Abstract: Tetherin is a host defense factor that physically prevents virion release from the plasma membrane. The Nef accessory protein of simian immunodeficiency virus (SIV) engages the clathrin adaptor AP-2 to downregulate tetherin via its DIWK motif. As human tetherin lacks DIWK, antagonism of tetherin by Nef is a barrier to simian-human transmission of non-human primate lentiviruses. To determine the molecular basis for tetherin counteraction, we reconstituted the AP-2 complex with a simian tetherin and SIV Nef and determined its structure by cryoelectron microscopy (cryo-EM). Nef refolds the first α-helix of the β2 subunit of AP-2 to a β hairpin, creating a binding site for the DIWK sequence. The tetherin binding site in Nef is distinct from those of most other Nef substrates, including MHC class I, CD3, and CD4 but overlaps with the site for the restriction factor SERINC5. This structure explains the dependence of SIVs on tetherin DIWK and consequent barrier to human transmission.

PubMed: 31447307
DOI: 10.1016/j.chom.2019.08.002

実験手法

ELECTRON MICROSCOPY (3.8 Å)