6YUC
Crystal structure of Uba4-Urm1 from Chaetomium thermophilum
Summary for 6YUC
| Entry DOI | 10.2210/pdb6yuc/pdb |
| Descriptor | Adenylyltransferase and sulfurtransferase uba4, Ubiquitin-related modifier 1, ZINC ION (3 entities in total) |
| Functional Keywords | ubiquitin-like protein activator 4, transferase |
| Biological source | Chaetomium thermophilum More |
| Total number of polymer chains | 2 |
| Total formula weight | 43752.99 |
| Authors | Grudnik, P.,Pabis, M.,Ethiraju Ravichandran, K.,Glatt, S. (deposition date: 2020-04-26, release date: 2020-07-22, Last modification date: 2024-11-06) |
| Primary citation | Pabis, M.,Termathe, M.,Ravichandran, K.E.,Kienast, S.D.,Krutyholowa, R.,Sokolowski, M.,Jankowska, U.,Grudnik, P.,Leidel, S.A.,Glatt, S. Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system in tRNA thiolation and ubiquitin-like conjugation. Embo J., 39:e105087-e105087, 2020 Cited by PubMed 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 (U ). 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. PubMed: 32901956DOI: 10.15252/embj.2020105087 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.15 Å) |
Structure validation
Download full validation report
