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 for Parkinson's disease-linked LRRK2's binding to microtubules.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 29, Issue 12, Page 1196-1207, Year 2022
掲載日	2022年12月12日
著者	David M Snead / Mariusz Matyszewski / Andrea M Dickey / Yu Xuan Lin / Andres E Leschziner / Samara L Reck-Peterson /
PubMed 要旨	Leucine-rich repeat kinase 2 (LRRK2) is one of the most commonly mutated genes in familial Parkinson's disease (PD). Under some circumstances, LRRK2 co-localizes with microtubules in cells, an ...Leucine-rich repeat kinase 2 (LRRK2) is one of the most commonly mutated genes in familial Parkinson's disease (PD). Under some circumstances, LRRK2 co-localizes with microtubules in cells, an association enhanced by PD mutations. We report a cryo-EM structure of the catalytic half of LRRK2, containing its kinase, in a closed conformation, and GTPase domains, bound to microtubules. We also report a structure of the catalytic half of LRRK1, which is closely related to LRRK2 but is not linked to PD. Although LRRK1's structure is similar to that of LRRK2, we find that LRRK1 does not interact with microtubules. Guided by these structures, we identify amino acids in LRRK2's GTPase that mediate microtubule binding; mutating them disrupts microtubule binding in vitro and in cells, without affecting LRRK2's kinase activity. Our results have implications for the design of therapeutic LRRK2 kinase inhibitors.
リンク	Nat Struct Mol Biol / PubMed:36510024 / PubMed Central
手法	EM (らせん対称) / EM (単粒子)
解像度	4.5 - 18.0 Å
構造データ	EMDB-25649: Helical Reconstruction of the C-terminal Half of Leucine Rich Repeat Kinase 2 (LRRK2) (I2020T) bound to 11-protofilament microtubule in presence of MLi-2 kinase inhibitor 手法: EM (らせん対称) / 解像度: 18.0 Å EMDB-25658: Local refinement of the C-terminal Half of Leucine Rich Repeat Kinase 2 (LRRK2) (I2020T) bound to 11-protofilament microtubule in presence of MLi-2 kinase inhibitor 手法: EM (単粒子) / 解像度: 6.6 Å EMDB-25664: Local Refinement of the C-terminal Half of Leucine Rich Repeat Kinase 2 (LRRK2) (I2020T) tetramer bound to 11-protofilament microtubule in presence of MLi-2 kinase inhibitor 手法: EM (単粒子) / 解像度: 5.9 Å EMDB-25672: Structure of the C-terminal half of Leucine Rich Repeat Kinase 1 (LRRK1) 手法: EM (単粒子) / 解像度: 5.8 Å EMDB-25674: Local refinement of the C-terminal Half of Leucine Rich Repeat Kinase 2 (LRRK2) (I2020T) bound to 12-protofilament microtubule without kinase inhibitors present 手法: EM (単粒子) / 解像度: 7.0 Å EMDB-25897: Local refinement of the C-terminal Half of Leucine Rich Repeat Kinase 2 (LRRK2) (I2020T) bound to 11-protofilament microtubule focused on the monomer in presence of MLi-2 kinase inhibitor 手法: EM (単粒子) / 解像度: 4.5 Å 25906 7thy EMDB-25906, PDB-7thy: Structure of Leucine Rich Repeat Kinase 2's ROC domain interacting with the microtubule facing the minus end 手法: EM (単粒子) / 解像度: 5.2 Å 25907 7thz EMDB-25907, PDB-7thz: Structure of Leucine Rich Repeat Kinase 2's ROC domain interacting with the microtubule facing the plus end 手法: EM (単粒子) / 解像度: 5.0 Å EMDB-25908: 2 microtubule protofilaments locally refined from Leucine Rich Repeat Kinase 2 filament structure bound to 11-protofilament microtubules 手法: EM (単粒子) / 解像度: 5.4 Å
化合物	ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP / GDP, エネルギー貯蔵分子*YM / グアノシン二リン酸
由来	homo sapiens (ヒト) Bos taurus (ウシ)
キーワード	CYTOSOLIC PROTEIN (細胞質基質) / parkinson's disease (パーキンソン病) / microtubule (微小管) / kinase (キナーゼ) / gtpase (GTPアーゼ)