9dns
Cryo-EM structure of Tom1-UBE2D2-ubiquitin complex
Structural highlights
FunctionTOM1_YEAST Probable ubiquitin ligase protein involved in many cellular processes, such as transcription regulation, maintenance of nuclear structure, cell cycle, mRNA export and rRNA maturation. E3 ubiquitin ligase proteins mediate ubiquitination and subsequent proteasomal degradation of target proteins. Involved in transcription regulation by interacting, and probably mediating, ubiquitination of some subunit of the SAGA complex. Required for SPT7 ubiquitination. Participates in mRNA export from the nucleus by regulating the transport of hnRNP proteins. Required for the shuttling of hnRNP protein NAB2, probably by mediating ubiquitination of a protein associated with NAB2. Also required for full induction of the general stress and heat-shock responses. Involved in 18S rRNA maturation by affecting several early steps in the rRNA processing pathway.[1] [2] [3] [4] [5] Publication Abstract from PubMedHomologous 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. Structural ubiquitin contributes to K48 linkage specificity of the HECT ligase Tom1.,Warner K, Hunkeler M, Baek K, Schmoker A, Roy Burman SS, Overwijn D, Jin C, Donovan KA, Fischer ES Cell Rep. 2025 May 12;44(5):115688. doi: 10.1016/j.celrep.2025.115688. PMID:40359109[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
