3NWH

Crystal structure of BST2/Tetherin

「3MKX」から置き換えられました

3NWH の概要

• エントリーDOI: 10.2210/pdb3nwh/pdb
• 関連するPDBエントリー: 2XG7
• 分子名称: Bone marrow stromal antigen 2 (2 entities in total)
• 機能のキーワード: coiled-coil, innate immunity, antiviral protein
• 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: 4
• 化学式量合計: 50430.93

構造登録者

Schubert, H.L.,Zhai, Q.,Hill, C.P. (登録日: 2010-07-09, 公開日: 2010-07-21, 最終更新日: 2024-11-27)

主引用文献

Schubert, H.L.,Zhai, Q.,Sandrin, V.,Eckert, D.M.,Garcia-Maya, M.,Saul, L.,Sundquist, W.I.,Steiner, R.A.,Hill, C.P.
Structural and functional studies on the extracellular domain of BST2/tetherin in reduced and oxidized conformations.
Proc.Natl.Acad.Sci.USA, 107:17951-17956, 2010

PubMed Abstract: HIV-1 and other enveloped viruses can be restricted by a host cellular protein called BST2/tetherin that prevents release of budded viruses from the cell surface. Mature BST2 contains a small cytosolic region, a predicted transmembrane helix, and an extracellular domain with a C-terminal GPI anchor. To advance understanding of BST2 function, we have determined a 2.6 Å crystal structure of the extracellular domain of the bacterially expressed recombinant human protein, residues 47-152, under reducing conditions. The structure forms a single long helix that associates as a parallel dimeric coiled coil over its C-terminal two-thirds, while the N-terminal third forms an antiparallel four-helix bundle with another dimer, creating a global tetramer. We also report the 3.45 Å resolution structure of BST2(51-151) prepared by expression as a secreted protein in HEK293T cells. This oxidized construct forms a dimer in the crystal that is superimposable with the reduced protein over the C-terminal two-thirds of the molecule, and its N terminus suggests pronounced flexibility. Hydrodynamic data demonstrated that BST2 formed a stable tetramer under reducing conditions and a dimer when oxidized to form disulfide bonds. A mutation that selectively disrupted the tetramer (L70D) increased protein expression modestly but only reduced antiviral activity by approximately threefold. Our data raise the possibility that BST2 may function as a tetramer at some stage, such as during trafficking, and strongly support a model in which the primary functional state of BST2 is a parallel disulfide-bound coiled coil that displays flexibility toward its N terminus.

PubMed: 20880831
DOI: 10.1073/pnas.1008206107

実験手法

X-RAY DIFFRACTION (2.6 Å)