9DNS
Cryo-EM structure of Tom1-UBE2D2-ubiquitin complex
Summary for 9DNS
| Entry DOI | 10.2210/pdb9dns/pdb |
| EMDB information | 47057 |
| Descriptor | E3 ubiquitin-protein ligase TOM1, Ubiquitin-conjugating enzyme E2 D2, Ubiquitin (3 entities in total) |
| Functional Keywords | transferase, ubiquitin, ubiquitylation, ligase, transferase-ligase complex, transferase/ligase |
| Biological source | Saccharomyces cerevisiae (brewer's yeast) More |
| Total number of polymer chains | 7 |
| Total formula weight | 445518.54 |
| Authors | Warner, K.M.,Hunkeler, M.,Baek, K.,Roy Burman, S.S.,Fischer, E.S. (deposition date: 2024-09-18, release date: 2025-05-28) |
| Primary citation | Warner, K.,Hunkeler, M.,Baek, K.,Schmoker, A.,Roy Burman, S.S.,Overwijn, D.,Jin, C.,Donovan, K.A.,Fischer, E.S. Structural ubiquitin contributes to K48 linkage specificity of the HECT ligase Tom1. Cell Rep, 44:115688-115688, 2025 Cited by PubMed Abstract: Homologous to E6AP C terminus (HECT) ubiquitin ligases play key roles in essential pathways such as DNA repair, cell cycle control, or protein quality control. Tom1 is one of five HECT ubiquitin E3 ligases in budding yeast S. cerevisiae and is prototypical for a ligase with pleiotropic functions such as ubiquitin chain amplification, orphan quality control, and DNA damage response. Structures of full-length HECT ligases, including the Tom1 ortholog HUWE1, have been reported, but how domains beyond the conserved catalytic module contribute to catalysis remains largely elusive. Here, through cryoelectron microscopy (cryo-EM) snapshots of Tom1 during an active ubiquitination cycle, we demonstrate that the extended domain architecture directly contributes to activity. We identify a Tom1-ubiquitin architecture during ubiquitination involving a non-canonical ubiquitin-binding site in the solenoid shape of Tom1. We demonstrate that this ubiquitin-binding site coordinates a structural ubiquitin contributing to the fidelity of K48 poly-ubiquitin chain assembly. PubMed: 40359109DOI: 10.1016/j.celrep.2025.115688 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.8 Å) |
Structure validation
Download full validation report
