EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Molecular Basis for RNA Cytidine Acetylation by NAT10.
ジャーナル・号・ページ	bioRxiv, Year 2024
掲載日	2024年3月27日
著者	Mingyang Zhou / Supuni Thalalla Gamage / Khoa A Tran / David Bartee / Xuepeng Wei / Boyu Yin / Shelley Berger / Jordan L Meier / Ronen Marmorstein
PubMed 要旨	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.
リンク	bioRxiv / PubMed:38585770 / PubMed Central
手法	EM (単粒子)
解像度	3.02 - 3.29 Å
構造データ	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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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+. 手法: EM (単粒子) / 解像度: 3.02 Å
化合物	PDB-1ahn: E. COLI FLAVODOXIN AT 2.6 ANGSTROMS RESOLUTION ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM PDB-1ah4: PIG ALDOSE REDUCTASE, HOLO FORM ChemComp-MG*: Unknown entry / マグネシウムジカチオン
由来	thermochaetoides thermophila dsm 1495 (菌類) chaetomium thermophilum (strain dsm 1495 / cbs 144.50 / imi 039719) (菌類)
キーワード	RNA BINDING PROTEIN / ac4C modification / RNA acetyltransferase