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	Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors.
ジャーナル・号・ページ	Nat Commun, Vol. 12, Issue 1, Page 4491, Year 2021
掲載日	2021年7月23日
著者	Constantin Cretu / Patricia Gee / Xiang Liu / Anant Agrawal / Tuong-Vi Nguyen / Arun K Ghosh / Andrew Cook / Melissa Jurica / Nicholas A Larsen / Vladimir Pena /
PubMed 要旨	Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing ...Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)-a complex chaperoning the selection of branch and 3' splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept.
リンク	Nat Commun / PubMed:34301950 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	2.4 - 3.1 Å
構造データ	12994 7onb EMDB-12994, PDB-7onb: Structure of the U2 5' module of the A3'-SSA complex 手法: EM (単粒子) / 解像度: 3.1 Å PDB-7b0i: Structure of a minimal SF3B core in complex with spliceostatin A (form II) 手法: X-RAY DIFFRACTION / 解像度: 3 Å PDB-7b91: Structure of a minimal SF3B core in complex with pladienolide D (form I) 手法: X-RAY DIFFRACTION / 解像度: 3 Å PDB-7b92: Structure of a minimal SF3B core in complex with sudemycin D6 (form II) 手法: X-RAY DIFFRACTION / 解像度: 3 Å PDB-7b9c: Structure of a minimal SF3B core in complex with spliceostatin A (form I) 手法: X-RAY DIFFRACTION / 解像度: 2.4 Å PDB-7omf: Structure of a minimal SF3B core in complex with sudemycin D6 (form I) 手法: X-RAY DIFFRACTION / 解像度: 3 Å PDB-7opi: Structure of a minimal SF3B core in complex with the inactive modulator spliceostatin E (form I) 手法: X-RAY DIFFRACTION / 解像度: 3.1 Å
化合物	ChemComp-SJT: spliceostatin A (form II) ChemComp-ZN: Unknown entry ChemComp-HOH: WATER ChemComp-T2Z: [(2~{S},3~{S},4~{E},6~{S},7~{R},10~{R})-3,7-dimethyl-2-[(2~{E},4~{E},6~{R})-6-methyl-6-oxidanyl-7-[(2~{R},3~{R})-3-[(2~{R},3~{S})-3-oxidanylpentan-2-yl]oxiran-2-yl]hepta-2,4-dien-2-yl]-7,10-bis(oxidanyl)-12-oxidanylidene-1-oxacyclododec-4-en-6-yl] ethanoate / プラジエノリドD ChemComp-T2W: [(~{Z},2~{S})-5-[[4-[(2~{E},4~{E})-3-methyl-5-[(2~{S},4~{R})-4,6,6-trimethyl-4-oxidanyl-oxan-2-yl]penta-2,4-dienyl]cyclohexyl]amino]-5-oxidanylidene-pent-3-en-2-yl] ~{N}-methylcarbamate ChemComp-SCN: THIOCYANATE ION / チオシアン酸アニオン ChemComp-07I: Spliceostatin E (form I) / スプリセオスタチンE
由来	homo sapiens (ヒト) unidentified adenovirus (ウイルス) human (ヒト) mus musculus (ハツカネズミ)
キーワード	SPLICING / SF3B / pre-mRNA splicing / splicing modulator / spliceostatin A / pladienolide D / sudemycin D6 / Splicing inhibitor / SF3B complex / Spliceosome / spliceostatin E