7ZRZ
Structure of the human tRNA splicing endonuclease defines substrate recognition
This is a non-PDB format compatible entry.
Summary for 7ZRZ
| Entry DOI | 10.2210/pdb7zrz/pdb |
| EMDB information | 14923 |
| Descriptor | tRNA-splicing endonuclease subunit Sen34, tRNA-splicing endonuclease subunit Sen2, tRNA-splicing endonuclease subunit Sen54, ... (5 entities in total) |
| Functional Keywords | rnp, endonuclease, trna, splicing, rna binding protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 144131.42 |
| Authors | Sekulovski, S.,Trowitzsch, S. (deposition date: 2022-05-05, release date: 2023-05-17, Last modification date: 2024-07-24) |
| Primary citation | Sekulovski, S.,Susac, L.,Stelzl, L.S.,Tampe, R.,Trowitzsch, S. Structural basis of substrate recognition by human tRNA splicing endonuclease TSEN. Nat.Struct.Mol.Biol., 30:834-840, 2023 Cited by PubMed Abstract: Heterotetrameric human transfer RNA (tRNA) splicing endonuclease TSEN catalyzes intron excision from precursor tRNAs (pre-tRNAs), utilizing two composite active sites. Mutations in TSEN and its associated RNA kinase CLP1 are linked to the neurodegenerative disease pontocerebellar hypoplasia (PCH). Despite the essential function of TSEN, the three-dimensional assembly of TSEN-CLP1, the mechanism of substrate recognition, and the structural consequences of disease mutations are not understood in molecular detail. Here, we present single-particle cryogenic electron microscopy reconstructions of human TSEN with intron-containing pre-tRNAs. TSEN recognizes the body of pre-tRNAs and pre-positions the 3' splice site for cleavage by an intricate protein-RNA interaction network. TSEN subunits exhibit large unstructured regions flexibly tethering CLP1. Disease mutations localize far from the substrate-binding interface and destabilize TSEN. Our work delineates molecular principles of pre-tRNA recognition and cleavage by human TSEN and rationalizes mutations associated with PCH. PubMed: 37231152DOI: 10.1038/s41594-023-00992-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.09 Å) |
Structure validation
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