7MDL
High-resolution crystal structure of human SepSecS-tRNASec complex
Summary for 7MDL
| Entry DOI | 10.2210/pdb7mdl/pdb |
| Descriptor | O-phosphoseryl-tRNA(Sec) selenium transferase, RNA (90-MER), (5-HYDROXY-4,6-DIMETHYLPYRIDIN-3-YL)METHYL DIHYDROGEN PHOSPHATE, ... (5 entities in total) |
| Functional Keywords | selenocysteine synthesis, protein translation, plp-dependent enzyme, rna binding, transferase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 262375.13 |
| Authors | Puppala, A.,French, R.L.,Simonovic, M. (deposition date: 2021-04-05, release date: 2022-11-09, Last modification date: 2024-11-06) |
| Primary citation | Puppala, A.K.,Castillo Suchkou, J.,French, R.L.,Kiernan, K.A.,Simonovic, M. Structural basis for the tRNA-dependent activation of the terminal complex of selenocysteine synthesis in humans. Nucleic Acids Res., 2023 Cited by PubMed Abstract: O-Phosphoseryl-tRNASec selenium transferase (SepSecS) catalyzes the terminal step of selenocysteine (Sec) synthesis in archaea and eukaryotes. How the Sec synthetic machinery recognizes and discriminates tRNASec from the tRNA pool is essential to the integrity of the selenoproteome. Previously, we suggested that SepSecS adopts a competent conformation that is pre-ordered for catalysis. Herein, using high-resolution X-ray crystallography, we visualized tRNA-dependent conformational changes in human SepSecS that may be a prerequisite for achieving catalytic competency. We show that tRNASec binding organizes the active sites of the catalytic protomer, while stabilizing the N- and C-termini of the non-catalytic protomer. Binding of large anions to the catalytic groove may further optimize the catalytic site for substrate binding and catalysis. Our biochemical and mutational analyses demonstrate that productive SepSecS•tRNASec complex formation is enthalpically driven and primarily governed by electrostatic interactions between the acceptor-, TΨC-, and variable arms of tRNASec and helices α1 and α14 of SepSecS. The detailed visualization of the tRNA-dependent activation of SepSecS provides a structural basis for a revised model of the terminal reaction of Sec formation in archaea and eukaryotes. PubMed: 36929010DOI: 10.1093/nar/gkad182 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.32 Å) |
Structure validation
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