6UPS
Crystal structure of the deubiquitylase domain from the Orientia tsutsugamushi protein OTT_1962 (OtDUB)
Summary for 6UPS
| Entry DOI | 10.2210/pdb6ups/pdb |
| Descriptor | ULP_PROTEASE domain-containing protein (2 entities in total) |
| Functional Keywords | deubiquitylase, orientia, ce clan, hydrolase |
| Biological source | Orientia tsutsugamushi (strain Ikeda) (Rickettsia tsutsugamushi) |
| Total number of polymer chains | 1 |
| Total formula weight | 29597.37 |
| Authors | Ronau, J.A.,Lim, C.S.,Xiong, Y. (deposition date: 2019-10-18, release date: 2020-04-01, Last modification date: 2024-11-06) |
| Primary citation | 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 Cited by 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: 32393759DOI: 10.1038/s41467-020-15985-4 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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