5JQS

Crystal structure of deubiquitinase MINDY-1 in complex with Ubiquitin

Summary for 5JQS

• Entry DOI: 10.2210/pdb5jqs/pdb
• Descriptor: Protein FAM63A, Ubiquitin-40S ribosomal protein S27a, prop-2-en-1-amine, ... (7 entities in total)
• Functional Keywords: hydrolase, cysteine protease, isopeptidase and ubiquitin binding
• Biological source: Homo sapiens (Human); More
• Cellular location: Ubiquitin: Cytoplasm : P62992
• Total number of polymer chains: 2
• Total formula weight: 41083.89

Authors

Abdul Rehman, S.A.,Kulathu, Y. (deposition date: 2016-05-05, release date: 2016-06-22, Last modification date: 2024-02-07)

Primary citation

Abdul Rehman, S.A.,Kristariyanto, Y.A.,Choi, S.Y.,Nkosi, P.J.,Weidlich, S.,Labib, K.,Hofmann, K.,Kulathu, Y.
MINDY-1 Is a Member of an Evolutionarily Conserved and Structurally Distinct New Family of Deubiquitinating Enzymes.
Mol.Cell, 63:146-155, 2016

PubMed 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.

PubMed: 27292798
DOI: 10.1016/j.molcel.2016.05.009

Experimental method

X-RAY DIFFRACTION (2.65 Å)