6DRM

OTU domain of Fam105A

Summary for 6DRM

• Entry DOI: 10.2210/pdb6drm/pdb
• Descriptor: Inactive ubiquitin thioesterase FAM105A (2 entities in total)
• Functional Keywords: fam105a, otupseu, deubiquitinase, otu domain, pseudo-enzyme, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 32731.77

Authors

Ceccarelli, D.F.,Sicheri, F.,Cordes, S. (deposition date: 2018-06-12, release date: 2019-05-08, Last modification date: 2023-10-11)

Primary citation

Ceccarelli, D.F.,Ivantsiv, S.,Mullin, A.A.,Coyaud, E.,Manczyk, N.,Maisonneuve, P.,Kurinov, I.,Zhao, L.,Go, C.,Gingras, A.C.,Raught, B.,Cordes, S.,Sicheri, F.
FAM105A/OTULINL Is a Pseudodeubiquitinase of the OTU-Class that Localizes to the ER Membrane.
Structure, 27:1000-1012.e6, 2019

PubMed Abstract: Pseudoenzymes have been identified across a diverse range of enzyme classes and fulfill important cellular functions. Examples of pseudoenzymes exist within ubiquitin conjugating and deubiquitinase (DUB) protein families. Here we characterize FAM105A/OTULINL, the only putative pseudodeubiquitinase of the ovarian tumor protease (OTU domain) family in humans. The crystal structure of FAM105A revealed that the OTU domain possesses structural deficiencies in both active site and substrate-binding infrastructure predicted to impair normal DUB function. We confirmed the absence of catalytic function against all ubiquitin linkages and an inability of FAM105A to bind ubiquitin compared with catalytically active FAM105B/OTULIN. FAM105A co-localized with KDEL markers and Lamin B1 at the endoplasmic reticulum (ER) and nuclear envelope, respectively. Accordingly, the FAM105A interactome exhibited significant enrichment in proteins localized to the ER/outer nuclear, Golgi and vesicular membranes. In light of undetectable deubiquitinase activity, we posit that FAM105A/OTULINL functions through its ability to mediate protein-protein interactions.

PubMed: 31056421
DOI: 10.1016/j.str.2019.03.022

Experimental method

X-RAY DIFFRACTION (2.06 Å)