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PXD015802

PXD015802 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMolecular characterization of the eukaryotic Uba4/Urm1 system
DescriptionUbiquitin-like protein activator 4 (Uba4) is required for the thiolation of uridine bases in eukaryotic transfer RNA. Uba4 catalyzes the sequential adenylation and thiocarboxylation of the C-terminus of Ubiquitin related modifier 1 (Urm1), acting as a hybrid between an E1-like activating enzyme and a sulfur-transferase. Structural and mechanistic details of the eukaryotic Uba4 protein and its respective reaction intermediates remained elusive. Here, we report the high-resolution crystal structures of full length Uba4 from Chaetomium thermophilum and its heterodimeric complex with Urm1. The structures show, how the aligned adenylation and rhodanese-like domains of Uba4 orchestrate substrate binding and specifically recognize and activate Urm1 at its C-terminus. We use complementary assays in vitro and in vivo to functionally validate all our structural findings. Furthermore, we uncover that under oxidative stress the specific relay of catalytic cysteines, similar to E1-E2 cascades, protects Uba4 from covalent conjugation by its own product, namely thiocarboxylated Urm1.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:09:00.945.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterUrszula Jankowska
SpeciesList scientific name: Chaetomium thermophilum; NCBI TaxID: 209285;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-10-14 02:04:16ID requested
12020-07-14 05:43:45announced
22020-09-13 22:27:58announced2020-09-14: Updated publication reference for PubMed record(s): 32901956.
32024-10-22 05:09:03announced2024-10-22: Updated project metadata.
Publication List
Pabis M, Termathe M, Ravichandran KE, Kienast SD, Krutyho, ł, owa R, Soko, ł, owski M, Jankowska U, Grudnik P, Leidel SA, Glatt S, Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system in tRNA thiolation and ubiquitin-like conjugation. EMBO J, 39(19):e105087(2020) [pubmed]
10.15252/embj.2020105087;
Keyword List
curator keyword: Biological
submitter keyword: Uba4, urmylation, Urm1
Contact List
Urszula Jankowska
contact affiliationMalopolska Centre of Biotechnology (MCB), Jagiellonian University, Krakow, Poland
contact emailurszula.jankowska@uj.edu.pl
lab head
Urszula Jankowska
contact affiliationProteomics and Mass Spectrometry Core Facility, Malopolska Centre of Biotechnology, Jagiellonian University
contact emailurszula.jankowska@uj.edu.pl
dataset submitter
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Dataset FTP location
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PRIDE project URI
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