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MINDY-1 Is a Member of an Evolutionarily Conserved and Structurally Distinct New Family of Deubiquitinating Enzymes

DOI: 10.1016/j.molcel.2016.05.009 DOI Help

Authors: Syed arif Abdul rehman (University of Dundee, Diamond Light Source) , Yosua adi Kristariyanto (University of Dundee) , Soo-youn Choi (University of Dundee) , Pedro Junior Nkosi (University of Dundee) , Simone Weidlich (University of Dundee) , Karim Labib (University of Dundee) , Kay Hofmann (University of Cologne) , Yogesh Kulathu (University of Dundee)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Cell , VOL 63 , PAGES 146 - 155

State: Published (Approved)
Published: July 2016
Diamond Proposal Number(s): 10071

Open Access Open Access

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.

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Instruments: I02-Macromolecular Crystallography

Other Facilities: European Synchrotron Radiation Facility (ID29 and ID23-1)

Added On: 08/08/2016 16:38

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