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	Elucidation of multiple high-resolution states of human MutSβ by cryo-EM reveals interplay between ATP/ADP binding and heteroduplex DNA recognition.
ジャーナル・号・ページ	Nucleic Acids Res, Vol. 53, Issue 12, Year 2025
掲載日	2025年6月20日
著者	Jung-Hoon Lee / Maren Thomsen / Herwin Daub / Gabriel Thieulin-Pardo / Stefan Steinbacher / Agnieszka Sztyler / Vinay Dahiya / Tobias Neudegger / Celia Dominguez / Ravi R Iyer / Hilary A Wilkinson / Edith Monteagudo / Nikolay V Plotnikov / Dan P Felsenfeld / Tasir S Haque / Michael Finley / Julien Boudet / Thomas F Vogt / Brinda C Prasad /
PubMed 要旨	Human and mouse genetic studies have demonstrated a role for DNA mismatch repair (MMR) molecular machines in modulating the rate of somatic expansion of the huntingtin (HTT) CAG repeats, and onset ...Human and mouse genetic studies have demonstrated a role for DNA mismatch repair (MMR) molecular machines in modulating the rate of somatic expansion of the huntingtin (HTT) CAG repeats, and onset and progression of Huntington's Disease (HD). MutSβ, a key component of the MMR pathway, is a heterodimeric protein of MSH2 and MSH3 that recognizes and initiates the repair of extrahelical DNA extrusions. Loss-of-function of mouse Msh3 and reduced-expression alleles of human MSH3 lead to slower rates of somatic expansion and delayed disease onset in humans, signifying MSH3 as a promising therapeutic target for HD. Here we report biochemical and cryo-electron microscopy analyses of human MutSβ, demonstrating MutSβ undergoes conformational changes induced by nucleotide and DNA binding. We present multiple conformations of MutSβ including the DNA-free MutSβ compatible with precisely complementary base-paired homoduplex DNA binding, two distinct structures of MutSβ bound to (CAG)2 DNA, a sliding clamp form and a DNA-unbound, ATP-bound conformation. Along with evidence for novel conformational states adopted by MutSβ to initiate the MMR cascade, these structures provide a foundation for structure-guided drug discovery.
リンク	Nucleic Acids Res / PubMed:40613711 / PubMed Central
手法	EM (単粒子)
解像度	3.02 - 7.08 Å
構造データ	16964 8olx EMDB-16964, PDB-8olx: MutSbeta bound to (CAG)2 DNA (canonical form) 手法: EM (単粒子) / 解像度: 3.1 Å 16969 8om5 EMDB-16969, PDB-8om5: DNA-free open form of MutSbeta 手法: EM (単粒子) / 解像度: 3.52 Å 16971 8om9 EMDB-16971, PDB-8om9: MutSbeta bound to (CAG)2 DNA (open form) 手法: EM (単粒子) / 解像度: 3.32 Å 16972 8oma EMDB-16972, PDB-8oma: MutSbeta bound to 61bp homoduplex DNA 手法: EM (単粒子) / 解像度: 3.29 Å 16973 8omo EMDB-16973, PDB-8omo: DNA-unbound MutSbeta-ATP complex (bent clamp form) 手法: EM (単粒子) / 解像度: 3.43 Å 16974 8omq EMDB-16974, PDB-8omq: DNA-unbound MutSbeta-ATP complex (straight clamp form) 手法: EM (単粒子) / 解像度: 3.11 Å EMDB-16975: MutSbeta bound to homoduplex plasmid DNA 手法: EM (単粒子) / 解像度: 7.08 Å 19605 8rz7 EMDB-19605, PDB-8rz7: (CAG)2 DNA-bound MutSbeta in open form with kinked MSH2 clamp 手法: EM (単粒子) / 解像度: 3.37 Å 19606 8rz8 EMDB-19606, PDB-8rz8: MutSbeta-ATPgS with straight MSH2 clamp 手法: EM (単粒子) / 解像度: 3.06 Å 19607 8rz9 EMDB-19607, PDB-8rz9: MutSbeta-ATPgS with kinked MSH2 clamp 手法: EM (単粒子) / 解像度: 3.02 Å
化合物	ChemComp-MG: Unknown entry ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, エネルギー貯蔵分子YM ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, エネルギー貯蔵分子YM ChemComp-AGS: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, エネルギー貯蔵分子類似体*YM
由来	homo sapiens (ヒト) synthetic construct (人工物)
キーワード	DNA BINDING PROTEIN / PROTEROS BIOSTRUCTURES GMBH / Protein-DNA complex / DNA repair protein complex / DNA REPAIR / MISMATCH RECOGNITION / ABC FAMILY ATPASE