Mol Cell. 2016 Jul 7;63(1):146-55. doi: 10.1016/j.molcel.2016.05.009. Epub 2016 Jun 9.
MINDY-1 Is a Member of an Evolutionarily Conserved and Structurally Distinct New Family of Deubiquitinating Enzymes.
Abdul Rehman SA1, Kristariyanto YA1, Choi SY1, Nkosi PJ1, Weidlich S1, Labib K1, Hofmann K2, Kulathu Y3.
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.
Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
Comment in
- PMID:
- 27292798
- PMCID:
- PMC4942677
- DOI:
- 10.1016/j.molcel.2016.05.009
- [Indexed for MEDLINE]
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