Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Molecular Basis for RNA Cytidine Acetylation by NAT10.
Journal, issue, pages	bioRxiv, Year 2024
Publish date	Mar 27, 2024
Authors	Mingyang Zhou / Supuni Thalalla Gamage / Khoa A Tran / David Bartee / Xuepeng Wei / Boyu Yin / Shelley Berger / Jordan L Meier / Ronen Marmorstein
PubMed Abstract	Human NAT10 acetylates the N4 position of cytidine in RNA, predominantly on rRNA and tRNA, to facilitate ribosome biogenesis and protein translation. NAT10 has been proposed as a therapeutic target ...Human NAT10 acetylates the N4 position of cytidine in RNA, predominantly on rRNA and tRNA, to facilitate ribosome biogenesis and protein translation. NAT10 has been proposed as a therapeutic target in cancers as well as aging-associated pathologies such as Hutchinson-Gilford Progeria Syndrome (HGPS). The ∼120 kDa NAT10 protein uses its acetyl-CoA-dependent acetyltransferase, ATP-dependent helicase, and RNA binding domains in concert to mediate RNA-specific N4-cytidine acetylation. While the biochemical activity of NAT10 is well known, the molecular basis for catalysis of eukaryotic RNA acetylation remains relatively undefined. To provide molecular insights into the RNA-specific acetylation by NAT10, we determined the single particle cryo-EM structures of NAT10 ( NAT10) bound to a bisubstrate cytidine-CoA probe with and without ADP. The structures reveal that NAT10 forms a symmetrical heart-shaped dimer with conserved functional domains surrounding the acetyltransferase active sites harboring the cytidine-CoA probe. Structure-based mutagenesis with analysis of mutants supports the catalytic role of two conserved active site residues (His548 and Tyr549 in NAT10), and two basic patches, both proximal and distal to the active site for RNA-specific acetylation. Yeast complementation analyses and senescence assays in human cells also implicates NAT10 catalytic activity in yeast thermoadaptation and cellular senescence. Comparison of the NAT10 structure to protein lysine and N-terminal acetyltransferase enzymes reveals an unusually open active site suggesting that these enzymes have been evolutionarily tailored for RNA recognition and cytidine-specific acetylation.
External links	bioRxiv / PubMed:38585770 / PubMed Central
Methods	EM (single particle)
Resolution	3.02 - 3.29 Å
Structure data	43996 9aym EMDB-43996, PDB-9aym: Cryo-EM Structure of E.coli produced recombinant N-acetyltransferase 10 (NAT10) in complex with cytidine-acetone-CoA bisubstrate probe Method: EM (single particle) / Resolution: 3.29 Å 44038 9b0e EMDB-44038: Cryo-EM Structure of E.coli produced recombinant N-acetyltransferase 10 (NAT10) in complex with cytidine-amide-CoA bisubstrate probe and ADP. PDB-9b0e: Cryo-EM Structure of E.coli produced recombinant N-acetyltransferase 10 (NAT10) in complex with cytidine-amide-CoA bisubstrate probe and ADP Method: EM (single particle) / Resolution: 3.19 Å 44042 9b0i EMDB-44042, PDB-9b0i: Cryo-EM Structure of Sf9 produced recombinant N-acetyltransferase 10 (NAT10) in complex with cytidine-amide-CoA bisubstrate probe and ADP/Mg2+. Method: EM (single particle) / Resolution: 3.02 Å
Chemicals	PDB-1ahn: E. COLI FLAVODOXIN AT 2.6 ANGSTROMS RESOLUTION ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM PDB-1ah4: PIG ALDOSE REDUCTASE, HOLO FORM ChemComp-MG*: Unknown entry
Source	thermochaetoides thermophila dsm 1495 (fungus) chaetomium thermophilum (strain dsm 1495 / cbs 144.50 / imi 039719) (fungus)
Keywords	RNA BINDING PROTEIN / ac4C modification / RNA acetyltransferase