9RMD

Human MINDY3 deubiquitinase (FAM188A)

Summary for 9RMD

• Entry DOI: 10.2210/pdb9rmd/pdb
• Descriptor: Ubiquitin carboxyl-terminal hydrolase MINDY-3 (2 entities in total)
• Functional Keywords: ubiquitin hydrolase, mindy3, k48, deubiquitinase, fam188a, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 49911.47

Authors

Krutyholowa, R.,Glatt, S. (deposition date: 2025-06-18, release date: 2026-06-17, Last modification date: 2026-07-22)

Primary citation

Armstrong, L.A.,McFarland, M.R.,O'Dea, R.,Krutyholowa, R.,Gorka, M.,Carroll, T.,Glatt, S.,Kulathu, Y.
The EF-hand domain of MINDY3 is a ubiquitin and RAD23 UBL-binding domain.
Embo Rep., 27:3604-3631, 2026

PubMed Abstract: The MINDY family of deubiquitinases (DUBs) are exemplified by their preference for cleaving K48-linked polyubiquitin. MINDY3 is architecturally distinct from other MINDY DUBs as its catalytic domain spans the entire length of the protein except for an atypical EF-hand insertion. We uncover this EF-hand (MINDY3) to be a ubiquitin-binding domain with three distinct binding sites, enabling MINDY3 to bind and effectively cleave long polyubiquitin chains. Furthermore, the MINDY3 domain binds not only to polyubiquitin but also to the UBL domain of the proteasome shuttling and DNA repair factors RAD23A and RAD23B. The MINDY3 facilitates this interaction with RAD23s in cells and mediates MINDY3 recruitment to DNA damage sites, establishing this unique DUB as a potential regulator of cellular DNA damage responses. MINDY3 binds specifically to the UBL domain of RAD23s, and none of the other UBLs tested. The crystal structure of the MINDY3:RAD23A domain complex reveals the molecular basis for specificity. We find that MINDY3 can form a ternary complex with RAD23A/B and polyubiquitin, and our findings suggest a model wherein MINDY3 can deubiquitylate RAD23A/B-bound clients.

PubMed: 42265305
DOI: 10.1038/s44319-026-00825-1

Experimental method

X-RAY DIFFRACTION (2.3 Å)