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-Structure paper
| タイトル | Structural mechanism of mRNA decoding by mammalian GTPase GTPBP1. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 17, Issue 1, Page 148, Year 2025 |
| 掲載日 | 2025年12月5日 |
著者 | Denis Susorov / Anna Miścicka / Dmitrij Golovenko / Anna B Loveland / Alexandra Zinoviev / Tatyana V Pestova / Andrei A Korostelev / ![]() |
| PubMed 要旨 | GTP-binding protein 1 (GTPBP1) is a widespread translational GTPase closely related to elongation factor eEF1A. The loss of GTPBP1 leads to neurodevelopmental and neurodegenerative disorders in ...GTP-binding protein 1 (GTPBP1) is a widespread translational GTPase closely related to elongation factor eEF1A. The loss of GTPBP1 leads to neurodevelopmental and neurodegenerative disorders in animals. Although linked to translation and quality control mechanisms, GTPBP1 molecular functions remain largely obscure. Similarly to eEF1A, GTPBP1 delivers aminoacyl-tRNA to the ribosome, but the ensuing GTPBP1-mediated elongation is slow. Here, using cryo-EM of mammalian 80S ribosomal complexes bound to GTPBP1 and aa-tRNA with GTP or the non-hydrolysable analog GDPCP, we show that the distinct GTPBP1 architecture and interactions with tRNA underlie slow GTPBP1 dissociation after GTP hydrolysis, resulting in delayed tRNA accommodation. Slow dissociation correlates with an extended proofreading stage and higher accuracy of GTPBP1-mediated decoding, potentially allowing GTPBP1 to elicit its putative quality control functions. GTPBP1 visualization provides the foundation for mapping and elucidating GTPBP1 mutations associated with human diseases. |
リンク | Nat Commun / PubMed:41350250 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.9 - 3.1 Å |
| 構造データ | EMDB-73297, PDB-9ypg: EMDB-73302, PDB-9ypo: EMDB-73307, PDB-9yps: EMDB-73308, PDB-9ypt: EMDB-73310, PDB-9ypv: EMDB-73311, PDB-9ypw: EMDB-73314, PDB-9ypy: EMDB-73315, PDB-9ypz: EMDB-73316, PDB-9yq0: EMDB-73317, PDB-9yq1: |
| 化合物 | ![]() ChemComp-SPD: ![]() ChemComp-ZN: ![]() ChemComp-GTP: ![]() ChemComp-PHE: ![]() ChemComp-ATP: ![]() ChemComp-MET: ![]() ChemComp-K: ![]() ChemComp-GCP: ![]() ChemComp-MG: ![]() ChemComp-GDP: |
| 由来 |
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キーワード | RIBOSOME / GTPBP1 / tRNA / GCP / complex |
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