6FFA

FMDV Leader protease bound to substrate ISG15

6FFA の概要

• エントリーDOI: 10.2210/pdb6ffa/pdb
• 分子名称: Lbpro, Ubiquitin-like protein ISG15, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: leader protease, deisgylase, deubiquitinase, hydrolase
• 由来する生物種: Foot-and-mouth disease virus; 詳細
• 細胞内の位置: Protein VP2: Virion. Protein VP3: Virion. Protein VP1: Virion. Protein 2B: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 2C: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 3A: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 3B-1: Virion . Protein 3B-2: Virion . Protein 3B-3: Virion . Picornain 3C: Host cytoplasm . RNA-directed RNA polymerase 3D-POL: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side : P03305; Cytoplasm : P05161
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28614.07

構造登録者

Swatek, K.N.,Pruneda, J.N.,Komander, D. (登録日: 2018-01-05, 公開日: 2018-02-21, 最終更新日: 2024-10-16)

主引用文献

Swatek, K.N.,Aumayr, M.,Pruneda, J.N.,Visser, L.J.,Berryman, S.,Kueck, A.F.,Geurink, P.P.,Ovaa, H.,van Kuppeveld, F.J.M.,Tuthill, T.J.,Skern, T.,Komander, D.
Irreversible inactivation of ISG15 by a viral leader protease enables alternative infection detection strategies.
Proc. Natl. Acad. Sci. U.S.A., 115:2371-2376, 2018

PubMed Abstract: In response to viral infection, cells mount a potent inflammatory response that relies on ISG15 and ubiquitin posttranslational modifications. Many viruses use deubiquitinases and deISGylases that reverse these modifications and antagonize host signaling processes. We here reveal that the leader protease, Lb, from foot-and-mouth disease virus (FMDV) targets ISG15 and to a lesser extent, ubiquitin in an unprecedented manner. Unlike canonical deISGylases that hydrolyze the isopeptide linkage after the C-terminal GlyGly motif, Lb cleaves the peptide bond preceding the GlyGly motif. Consequently, the GlyGly dipeptide remains attached to the substrate Lys, and cleaved ISG15 is rendered incompetent for reconjugation. A crystal structure of Lb bound to an engineered ISG15 suicide probe revealed the molecular basis for ISG15 proteolysis. Importantly, anti-GlyGly antibodies, developed for ubiquitin proteomics, are able to detect Lb cleavage products during viral infection. This opens avenues for infection detection of FMDV based on an immutable, host-derived epitope.

PubMed: 29463763
DOI: 10.1073/pnas.1710617115

実験手法

X-RAY DIFFRACTION (1.5 Å)