7YW3

Crystal structure of tRNA 2'-phosphotransferase from Homo sapiens

Summary for 7YW3

• Entry DOI: 10.2210/pdb7yw3/pdb
• Descriptor: tRNA 2'-phosphotransferase 1, [[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [(2~{R},3~{S},4~{R},5~{R})-3,4-bis(oxidanyl)-5-phosphonooxy-oxolan-2-yl]methyl hydrogen phosphate, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: trna 2'-phosphotransferase, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 28483.34

Authors

Yang, X.Y.,Liu, X.H. (deposition date: 2022-08-21, release date: 2023-07-26, Last modification date: 2023-08-30)

Primary citation

Yang, X.,Wang, J.,Li, S.,Li, X.,Gong, J.,Yan, Z.,Zhou, H.,Wu, C.,Liu, X.
Structural and biochemical insights into the molecular mechanism of TRPT1 for nucleic acid ADP-ribosylation.
Nucleic Acids Res., 51:7649-7665, 2023

PubMed Abstract: Nucleic acid ADP-ribosylation has been established as a novel modification found in a wide diversity of prokaryotic and eukaryotic organisms. tRNA 2'-phosphotransferase 1 (TRPT1/TPT1/KptA) possesses ADP-ribosyltransferase (ART) activity and is able to ADP-ribosylate nucleic acids. However, the underlying molecular mechanism remains elusive. Here, we determined crystal structures of TRPT1s in complex with NAD+ from Homo sapiens, Mus musculus and Saccharomyces cerevisiae. Our results revealed that the eukaryotic TRPT1s adopt common mechanisms for both NAD+ and nucleic acid substrate binding. The conserved SGR motif induces a significant conformational change in the donor loop upon NAD+ binding to facilitate the catalytic reaction of ART. Moreover, the nucleic acid-binding residue redundancy provides structural flexibility to accommodate different nucleic acid substrates. Mutational assays revealed that TRPT1s employ different catalytic and nucleic acid-binding residues to perform nucleic acid ADP-ribosylation and RNA 2'-phosphotransferase activities. Finally, cellular assays revealed that the mammalian TRPT1 is able to promote endocervical HeLa cell survival and proliferation. Together, our results provide structural and biochemical insights into the molecular mechanism of TRPT1 for nucleic acid ADP-ribosylation.

PubMed: 37334830
DOI: 10.1093/nar/gkad525

Experimental method

X-RAY DIFFRACTION (2.5 Å)