6Y6R
Crystal structure of MINDY1 T335D mutant
Summary for 6Y6R
| Entry DOI | 10.2210/pdb6y6r/pdb |
| Descriptor | Ubiquitin carboxyl-terminal hydrolase MINDY-1 (1 entity in total) |
| Functional Keywords | hydrolase, cysteine protease, isopeptidase and ubiquitin binding |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 32052.20 |
| Authors | Abdul Rehman, S.A.,Kulathu, Y. (deposition date: 2020-02-27, release date: 2021-03-31, Last modification date: 2024-01-24) |
| Primary citation | Abdul Rehman, S.A.,Armstrong, L.A.,Lange, S.M.,Kristariyanto, Y.A.,Grawert, T.W.,Knebel, A.,Svergun, D.I.,Kulathu, Y. Mechanism of activation and regulation of deubiquitinase activity in MINDY1 and MINDY2. Mol.Cell, 81:4176-4190.e6, 2021 Cited by PubMed Abstract: Of the eight distinct polyubiquitin (polyUb) linkages that can be assembled, the roles of K48-linked polyUb (K48-polyUb) are the most established, with K48-polyUb modified proteins being targeted for degradation. MINDY1 and MINDY2 are members of the MINDY family of deubiquitinases (DUBs) that have exquisite specificity for cleaving K48-polyUb, yet we have a poor understanding of their catalytic mechanism. Here, we analyze the crystal structures of MINDY1 and MINDY2 alone and in complex with monoUb, di-, and penta-K48-polyUb, identifying 5 distinct Ub binding sites in the catalytic domain that explain how these DUBs sense both Ub chain length and linkage type to cleave K48-polyUb chains. The activity of MINDY1/2 is inhibited by the Cys-loop, and we find that substrate interaction relieves autoinhibition to activate these DUBs. We also find that MINDY1/2 use a non-canonical catalytic triad composed of Cys-His-Thr. Our findings highlight multiple layers of regulation modulating DUB activity in MINDY1 and MINDY2. PubMed: 34529927DOI: 10.1016/j.molcel.2021.08.024 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.32 Å) |
Structure validation
Download full validation report
