8ORJ
Cryo-EM structure of human tRNA ligase RTCB in complex with human PYROXD1.
Summary for 8ORJ
| Entry DOI | 10.2210/pdb8orj/pdb |
| Related | 6ZK7 7P3B |
| EMDB information | 17127 |
| Descriptor | RNA-splicing ligase RtcB homolog, Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1, MAGNESIUM ION, ... (5 entities in total) |
| Functional Keywords | trna ligase, pyroxd1, rtcb, flavoprotein, ligase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 113072.91 |
| Authors | Loeff, L.,Kroupova, A.,Asanovic, I.,Boneberg, F.,Pfleiderer, M.M.,Ferdigg, A.,Ackle, F.,Martinez, J.,Jinek, M. (deposition date: 2023-04-14, release date: 2024-10-30, Last modification date: 2025-05-07) |
| Primary citation | Loeff, L.,Kroupova, A.,Asanovic, I.,Boneberg, F.M.,Pfleiderer, M.M.,Riermeier, L.,Leitner, A.,Ferdigg, A.,Ackle, F.,Martinez, J.,Jinek, M. Mechanistic basis for PYROXD1-mediated protection of the human tRNA ligase complex against oxidative inactivation. Nat.Struct.Mol.Biol., 2025 Cited by PubMed Abstract: The metazoan tRNA ligase complex (tRNA-LC) has essential roles in tRNA biogenesis and unfolded protein response. Its catalytic subunit RTCB contains a conserved active-site cysteine that is susceptible to metal ion-induced oxidative inactivation. The flavin-containing oxidoreductase PYROXD1 preserves the activity of human tRNA-LC in a NAD(P)H-dependent manner, but its protective mechanism remains elusive. Here, we report a cryogenic electron microscopic structure of the human RTCB-PYROXD1 complex, revealing that PYROXD1 directly interacts with the catalytic center of RTCB through its carboxy-terminal tail. NAD(P)H binding and FAD reduction allosterically control PYROXD1 activity and RTCB recruitment, while reoxidation of PYROXD1 enables timed release of RTCB. PYROXD1 interaction is mutually exclusive with Archease-mediated RTCB guanylylation, and guanylylated RTCB is intrinsically protected from oxidative inactivation. Together, these findings provide a mechanistic framework for the protective function of PYROXD1 that maintains the activity of the tRNA-LC under aerobic conditions. PubMed: 40069351DOI: 10.1038/s41594-025-01516-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.3 Å) |
Structure validation
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