6UPS

Crystal structure of the deubiquitylase domain from the Orientia tsutsugamushi protein OTT_1962 (OtDUB)

6UPS の概要

• エントリーDOI: 10.2210/pdb6ups/pdb
• 分子名称: ULP_PROTEASE domain-containing protein (2 entities in total)
• 機能のキーワード: deubiquitylase, orientia, ce clan, hydrolase
• 由来する生物種: Orientia tsutsugamushi (strain Ikeda) (Rickettsia tsutsugamushi)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29597.37

構造登録者

Ronau, J.A.,Lim, C.S.,Xiong, Y. (登録日: 2019-10-18, 公開日: 2020-04-01, 最終更新日: 2024-11-06)

主引用文献

Berk, J.M.,Lim, C.,Ronau, J.A.,Chaudhuri, A.,Chen, H.,Beckmann, J.F.,Loria, J.P.,Xiong, Y.,Hochstrasser, M.
A deubiquitylase with an unusually high-affinity ubiquitin-binding domain from the scrub typhus pathogen Orientia tsutsugamushi.
Nat Commun, 11:2343-2343, 2020

PubMed Abstract: Ubiquitin mediated signaling contributes critically to host cell defenses during pathogen infection. Many pathogens manipulate the ubiquitin system to evade these defenses. Here we characterize a likely effector protein bearing a deubiquitylase (DUB) domain from the obligate intracellular bacterium Orientia tsutsugamushi, the causative agent of scrub typhus. The Ulp1-like DUB prefers ubiquitin substrates over ubiquitin-like proteins and efficiently cleaves polyubiquitin chains of three or more ubiquitins. The co-crystal structure of the DUB (OtDUB) domain with ubiquitin revealed three bound ubiquitins: one engages the S1 site, the second binds an S2 site contributing to chain specificity and the third binds a unique ubiquitin-binding domain (UBD). The UBD modulates OtDUB activity, undergoes a pronounced structural transition upon binding ubiquitin, and binds monoubiquitin with an unprecedented ~5 nM dissociation constant. The characterization and high-resolution structure determination of this enzyme should aid in its development as a drug target to counter Orientia infections.

PubMed: 32393759
DOI: 10.1038/s41467-020-15985-4

実験手法

X-RAY DIFFRACTION (2 Å)