Universität zu Köln

Rehman, Syed Arif Abdul, Kristariyanto, Yosua Adi, Choi, Soo-Youn, Nkosi, Pedro Junior, Weidlich, Simone, Labib, Karim, Hofmann, Kay ORCID: 0000-0002-2289-9083 and Kulathu, Yogesh ORCID: 0000-0002-3274-1642 (2016). MINDY-1 Is a Member of an Evolutionarily Conserved and Structurally Distinct New Family of Deubiquitinating Enzymes. Mol. Cell, 63 (1). S. 146 - 156. CAMBRIDGE: CELL PRESS. ISSN 1097-4164

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Abstract

Deubiquitinating enzymes (DUBs) remove ubiquitin (Ub) from Ub-conjugated substrates to regulate the functional outcome of ubiquitylation. Here we report the discovery of a new family of DUBs, which we have named MINDY (motif interacting with Ub-containing novel DUB family). Found in all eukaryotes, MINDY-family DUBs are highly selective at cleaving K48-linked polyUb, a signal that targets proteins for degradation. We identify the catalytic activity to be encoded within a previously unannotated domain, the crystal structure of which reveals a distinct protein fold with no homology to any of the known DUBs. The crystal structure of MINDY-1 (also known as FAM63A) in complex with propargylated Ub reveals conformational changes that realign the active site for catalysis. MINDY-1 prefers cleaving long polyUb chains and works by trimming chains from the distal end. Collectively, our results reveal a new family of DUBs that may have specialized roles in regulating proteostasis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rehman, Syed Arif Abdul UNSPECIFIED UNSPECIFIED UNSPECIFIED Kristariyanto, Yosua Adi UNSPECIFIED UNSPECIFIED UNSPECIFIED Choi, Soo-Youn UNSPECIFIED UNSPECIFIED UNSPECIFIED Nkosi, Pedro Junior UNSPECIFIED UNSPECIFIED UNSPECIFIED Weidlich, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Labib, Karim UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Kay UNSPECIFIED orcid.org/0000-0002-2289-9083 UNSPECIFIED Kulathu, Yogesh UNSPECIFIED orcid.org/0000-0002-3274-1642 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-270093
DOI:	10.1016/j.molcel.2016.05.009
Journal or Publication Title:	Mol. Cell
Volume:	63
Number:	1
Page Range:	S. 146 - 156
Date:	2016
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4164
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 UBIQUITIN; PROTEIN; POLYUBIQUITIN; PROTEASOME; REVEALS; RECOGNITION; SPECIFICITY; BINDING; RABEX-5 Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27009