8HAE
Cryo-EM structure of HACE1 dimer
Summary for 8HAE
| Entry DOI | 10.2210/pdb8hae/pdb |
| EMDB information | 34586 |
| Descriptor | E3 ubiquitin-protein ligase HACE1 (1 entity in total) |
| Functional Keywords | e3 ubiquitin ligase, tumor suppressor, post-translational modifier, protein degradation, antitumor protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 204899.34 |
| Authors | Singh, S.,Machida, S.,Tulsian, N.K.,Choong, Y.K.,Ng, J.,Shanker, S.,Yaochen, L.D.,Shi, J.,Sivaraman, J.,Machida, S. (deposition date: 2022-10-26, release date: 2023-06-28, Last modification date: 2023-10-04) |
| Primary citation | Singh, S.,Machida, S.,Tulsian, N.K.,Choong, Y.K.,Ng, J.,Shankar, S.,Liu, Y.,Chandiramani, K.V.,Shi, J.,Sivaraman, J. Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization. Adv Sci, 10:e2207672-e2207672, 2023 Cited by PubMed Abstract: HACE1 is an ankyrin repeat (AKR) containing HECT-type E3 ubiquitin ligase that interacts with and ubiquitinates multiple substrates. While HACE1 is a well-known tumor suppressor, its structure and mode of ubiquitination are not understood. The authors present the cryo-EM structures of human HACE1 along with in vitro functional studies that provide insights into how the enzymatic activity of HACE1 is regulated. HACE1 comprises of an N-terminal AKR domain, a middle (MID) domain, and a C-terminal HECT domain. Its unique G-shaped architecture interacts as a homodimer, with monomers arranged in an antiparallel manner. In this dimeric arrangement, HACE1 ubiquitination activity is hampered, as the N-terminal helix of one monomer restricts access to the C-terminal domain of the other. The in vitro ubiquitination assays, hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis, mutagenesis, and in silico modeling suggest that the HACE1 MID domain plays a crucial role along with the AKRs in RAC1 substrate recognition. PubMed: 37537642DOI: 10.1002/advs.202207672 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.55 Å) |
Structure validation
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