6J1X
WWP1 close conformation
Summary for 6J1X
| Entry DOI | 10.2210/pdb6j1x/pdb |
| Descriptor | NEDD4-like E3 ubiquitin-protein ligase WWP1, GLYCEROL (3 entities in total) |
| Functional Keywords | e3 ligase, close conformation, autoinhibition, ligase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 65256.60 |
| Authors | Liu, Z.H. (deposition date: 2018-12-30, release date: 2019-07-24, Last modification date: 2023-11-22) |
| Primary citation | Wang, Z.,Liu, Z.,Chen, X.,Li, J.,Yao, W.,Huang, S.,Gu, A.,Lei, Q.Y.,Mao, Y.,Wen, W. A multi-lock inhibitory mechanism for fine-tuning enzyme activities of the HECT family E3 ligases. Nat Commun, 10:3162-3162, 2019 Cited by PubMed Abstract: HECT E3 ligases control the degradation and functioning of numerous oncogenic/tumor-suppressive factors and signaling proteins, and their activities must be tightly regulated to prevent cancers and other diseases. Here we show that the Nedd4 family HECT E3 WWP1 adopts an autoinhibited state, in which its multiple WW domains sequester HECT using a multi-lock mechanism. Removing WW2 or WW34 led to a partial activation of WWP1. The structure of fully inhibited WWP1 reveals that many WWP1 mutations identified in cancer patients result in a partially active state with increased E3 ligase activity, and the WWP1 mutants likely promote cell migration by enhancement of ∆Np63α degradation. We further demonstrate that WWP2 and Itch utilize a highly similar multi-lock autoinhibition mechanism as that utilized by WWP1, whereas Nedd4/4 L and Smurf2 utilize a slightly variant version. Overall, these results reveal versatile autoinhibitory mechanisms that fine-tune the ligase activities of the HECT family enzymes. PubMed: 31320636DOI: 10.1038/s41467-019-11224-7 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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