dc.contributor.author | Pabis, M | |
dc.contributor.author | Termathe, M | |
dc.contributor.author | Ravichandran, KE | |
dc.contributor.author | Kienast, SD | |
dc.contributor.author | Krutyhołowa, R | |
dc.contributor.author | Sokołowski, M | |
dc.contributor.author | Jankowska, U | |
dc.contributor.author | Grudnik, P | |
dc.contributor.author | Leidel, SA | |
dc.contributor.author | Glatt, S | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2023-05-19T09:54:58Z | |
dc.date.available | 2023-05-19T09:54:58Z | |
dc.date.issued | 2020-10-01 | |
dc.identifier | ARTN e105087 | |
dc.identifier.citation | The EMBO Journal, 2020, 39 (19), pp. e105087 - | |
dc.identifier.issn | 0261-4189 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5792 | |
dc.identifier.eissn | 1460-2075 | |
dc.identifier.eissn | 1460-2075 | |
dc.identifier.doi | 10.15252/embj.2020105087 | |
dc.description.abstract | The chemical modification of tRNA bases by sulfur is crucial to tune translation and to optimize protein synthesis. In eukaryotes, the ubiquitin-related modifier 1 (Urm1) pathway is responsible for the synthesis of 2-thiolated wobble uridine (U34 ). During the key step of the modification cascade, the E1-like activating enzyme ubiquitin-like protein activator 4 (Uba4) first adenylates and thiocarboxylates the C-terminus of its substrate Urm1. Subsequently, activated thiocarboxylated Urm1 (Urm1-COSH) can serve as a sulfur donor for specific tRNA thiolases or participate in ubiquitin-like conjugation reactions. Structural and mechanistic details of Uba4 and Urm1 have remained elusive but are key to understand the evolutionary branch point between ubiquitin-like proteins (UBL) and sulfur-relay systems. Here, we report the crystal structures of full-length Uba4 and its heterodimeric complex with its substrate Urm1. We show how the two domains of Uba4 orchestrate recognition, binding, and thiocarboxylation of the C-terminus of Urm1. Finally, we uncover how the catalytic domains of Uba4 communicate efficiently during the reaction cycle and identify a mechanism that enables Uba4 to protect itself against self-conjugation with its own product, namely activated Urm1-COSH. | |
dc.format | Print-Electronic | |
dc.format.extent | e105087 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | WILEY | |
dc.relation.ispartof | The EMBO Journal | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | adenylation | |
dc.subject | tRNA modification | |
dc.subject | thioester | |
dc.subject | thiolation | |
dc.subject | ubiquitin-like proteins | |
dc.subject | Humans | |
dc.subject | Nucleotidyltransferases | |
dc.subject | RNA, Transfer | |
dc.subject | Sulfur | |
dc.subject | Sulfurtransferases | |
dc.subject | Ubiquitins | |
dc.title | Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system in tRNA thiolation and ubiquitin-like conjugation. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-06-26 | |
dc.date.updated | 2023-05-19T09:50:31Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.15252/embj.2020105087 | |
rioxxterms.licenseref.startdate | 2020-10-01 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/32901956 | |
pubs.issue | 19 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Structural Biology of Cell Signalling | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.15252/embj.2020105087 | |
pubs.volume | 39 | |
icr.provenance | Deposited by Mr Keerthiraju Ethiraju Ravichandran on 2023-05-19. Deposit type is initial. No. of files: 1. Files: Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system in tRNA thiolation and ubiquitin-like conjugation.pdf | |