6FGE

Crystal structure of human ZUFSP/ZUP1 in complex with ubiquitin

Summary for 6FGE

• Entry DOI: 10.2210/pdb6fge/pdb
• Descriptor: Zinc finger with UFM1-specific peptidase domain protein, Polyubiquitin-B, MALONATE ION, ... (10 entities in total)
• Functional Keywords: hydrolase, cysteine protease, isopeptidase and ubiquitin binding
• Biological source: Homo sapiens (Human); More
• Cellular location: Ubiquitin: Cytoplasm : P0CG47
• Total number of polymer chains: 2
• Total formula weight: 49377.14

Authors

Kwasna, D.,Abdul Rehman, S.A.,Kulathu, Y. (deposition date: 2018-01-10, release date: 2018-04-04, Last modification date: 2018-04-18)

Primary citation

Kwasna, D.,Abdul Rehman, S.A.,Natarajan, J.,Matthews, S.,Madden, R.,De Cesare, V.,Weidlich, S.,Virdee, S.,Ahel, I.,Gibbs-Seymour, I.,Kulathu, Y.
Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability.
Mol. Cell, 70:150-164.e6, 2018

PubMed Abstract: Deubiquitinating enzymes (DUBs) are important regulators of ubiquitin signaling. Here, we report the discovery of deubiquitinating activity in ZUFSP/C6orf113. High-resolution crystal structures of ZUFSP in complex with ubiquitin reveal several distinctive features of ubiquitin recognition and catalysis. Our analyses reveal that ZUFSP is a novel DUB with no homology to any known DUBs, leading us to classify ZUFSP as the seventh DUB family. Intriguingly, the minimal catalytic domain does not cleave polyubiquitin. We identify two ubiquitin binding domains in ZUFSP: a ZHA (ZUFSP helical arm) that binds to the distal ubiquitin and an atypical UBZ domain in ZUFSP that binds to polyubiquitin. Importantly, both domains are essential for ZUFSP to selectively cleave K63-linked polyubiquitin. We show that ZUFSP localizes to DNA lesions, where it plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage.

PubMed: 29576527
DOI: 10.1016/j.molcel.2018.02.023

Experimental method

X-RAY DIFFRACTION (1.74 Å)