Universität zu Köln

Hermanns, Thomas ORCID: 0000-0001-5350-7479, Pichlo, Christian ORCID: 0000-0002-3156-5667, Woiwode, Ilka, Klopffleisch, Karsten ORCID: 0000-0002-6977-1386, Witting, Katharina F., Ovaa, Huib ORCID: 0000-0002-0068-054X, Baumann, Ulrich and Hofmann, Kay (2018). A family of unconventional deubiquitinases with modular chain specificity determinants. Nat. Commun., 9. BERLIN: NATURE RESEARCH. ISSN 2041-1723

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Abstract

Deubiquitinating enzymes (DUBs) regulate ubiquitin signaling by trimming ubiquitin chains or removing ubiquitin from modified substrates. Similar activities exist for ubiquitin-related modifiers, although the enzymes involved are usually not related. Here, we report human ZUFSP (also known as ZUP1 and C6orf113) and fission yeast Mug105 as founding members of a DUB family different from the six known DUB classes. The crystal structure of human ZUFSP in covalent complex with propargylated ubiquitin shows that the DUB family shares a fold with UFM1-and Atg8-specific proteases, but uses a different active site more similar to canonical DUB enzymes. ZUFSP family members differ widely in linkage specificity through differential use of modular ubiquitin-binding domains (UBDs). While the minimalistic Mug105 prefers K48 chains, ZUFSP uses multiple UBDs for its K63-specific endo-DUB activity. K63 specificity, localization, and protein interaction network suggest a role for ZUFSP in DNA damage response.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hermanns, Thomas UNSPECIFIED orcid.org/0000-0001-5350-7479 UNSPECIFIED Pichlo, Christian UNSPECIFIED orcid.org/0000-0002-3156-5667 UNSPECIFIED Woiwode, Ilka UNSPECIFIED UNSPECIFIED UNSPECIFIED Klopffleisch, Karsten UNSPECIFIED orcid.org/0000-0002-6977-1386 UNSPECIFIED Witting, Katharina F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ovaa, Huib UNSPECIFIED orcid.org/0000-0002-0068-054X UNSPECIFIED Baumann, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Kay UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-195610
DOI:	10.1038/s41467-018-03148-5
Journal or Publication Title:	Nat. Commun.
Volume:	9
Date:	2018
Publisher:	NATURE RESEARCH
Place of Publication:	BERLIN
ISSN:	2041-1723
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STRUCTURE REFINEMENT; STRUCTURAL BASIS; UBIQUITIN; REVEALS; BINDING; RECOGNITION; COMPLEX; ENABLES; DOMAIN Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19561