7E59

interferon-inducible anti-viral protein truncated

7E59 の概要

• エントリーDOI: 10.2210/pdb7e59/pdb
• 分子名称: Guanylate-binding protein 5 (1 entity in total)
• 機能のキーワード: interferon-induced, gtpase, anti-hiv, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 219706.09

構造登録者

Cui, W.,Wang, W.,Chen, C.,Slater, B.,Xiong, Y.,Ji, X.Y.,Yang, H.T. (登録日: 2021-02-18, 公開日: 2021-05-05, 最終更新日: 2023-11-29)

主引用文献

Cui, W.,Braun, E.,Wang, W.,Tang, J.,Zheng, Y.,Slater, B.,Li, N.,Chen, C.,Liu, Q.,Wang, B.,Li, X.,Duan, Y.,Xiao, Y.,Ti, R.,Hotter, D.,Ji, X.,Zhang, L.,Cui, J.,Xiong, Y.,Sauter, D.,Wang, Z.,Kirchhoff, F.,Yang, H.
Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: Guanylate-binding proteins (GBPs) form a family of dynamin-related large GTPases which mediate important innate immune functions. They were proposed to form oligomers upon GTP binding/hydrolysis, but the molecular mechanisms remain elusive. Here, we present crystal structures of C-terminally truncated human GBP5 (hGBP5), comprising the large GTPase (LG) and middle (MD) domains, in both its nucleotide-free monomeric and nucleotide-bound dimeric states, together with nucleotide-free full-length human GBP2. Upon GTP-loading, hGBP5 forms a closed face-to-face dimer. The MD of hGBP5 undergoes a drastic movement relative to its LG domain and forms extensive interactions with the LG domain and MD of the pairing molecule. Disrupting the MD interface (for hGBP5) or mutating the hinge region (for hGBP2/5) impairs their ability to inhibit HIV-1. Our results point to a GTP-induced dimerization mode that is likely conserved among all GBP members and provide insights into the molecular determinants of their antiviral function.

PubMed: 33876762
DOI: 10.1073/pnas.2022269118

実験手法

X-RAY DIFFRACTION (3 Å)