7UYH

Structure of the first OTU domain from Legionella pneumophila effector protein LotA bound to K6-linked diUb

Summary for 7UYH

• Entry DOI: 10.2210/pdb7uyh/pdb
• Descriptor: Ubiquitin, LotA (3 entities in total)
• Functional Keywords: deubiquitinase, otu, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 49043.67

Authors

Warren, G.D.,Pruneda, J.N. (deposition date: 2022-05-06, release date: 2022-12-21, Last modification date: 2023-10-25)

Primary citation

Warren, G.D.,Kitao, T.,Franklin, T.G.,Nguyen, J.V.,Geurink, P.P.,Kubori, T.,Nagai, H.,Pruneda, J.N.
Mechanism of Lys6 poly-ubiquitin specificity by the L. pneumophila deubiquitinase LotA.
Mol.Cell, 83:105-120.e5, 2023

PubMed Abstract: The versatility of ubiquitination to control vast domains of eukaryotic biology is due, in part, to diversification through differently linked poly-ubiquitin chains. Deciphering signaling roles for some chain types, including those linked via K6, has been stymied by a lack of specificity among the implicated regulatory proteins. Forged through strong evolutionary pressures, pathogenic bacteria have evolved intricate mechanisms to regulate host ubiquitin during infection. Herein, we identify and characterize a deubiquitinase domain of the secreted effector LotA from Legionella pneumophila that specifically regulates K6-linked poly-ubiquitin. We demonstrate the utility of LotA for studying K6 poly-ubiquitin signals. We identify the structural basis of LotA activation and poly-ubiquitin specificity and describe an essential "adaptive" ubiquitin-binding domain. Without LotA activity during infection, the Legionella-containing vacuole becomes decorated with K6 poly-ubiquitin as well as the AAA ATPase VCP/p97/Cdc48. We propose that LotA's deubiquitinase activity guards Legionella-containing vacuole components from ubiquitin-dependent extraction.

PubMed: 36538933
DOI: 10.1016/j.molcel.2022.11.022

Experimental method

X-RAY DIFFRACTION (2.8 Å)