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torsdag 4 juli 2019

Deubikitinaasien VI ryhmä MINDY trimmaa K48-linkkityneitä polyub-ketjuja ja säätelee proteostaasia

https://www.ncbi.nlm.nih.gov/pubmed/?term=MINDY++DUBs


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.

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.
PMID:
27292798
PMCID:
PMC4942677
DOI:
10.1016/j.molcel.2016.05.009
[Indexed for MEDLINE]
Free PMC Article

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