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 insights into the GTP-driven monomerization and activation of a bacterial LRRK2 homolog using allosteric nanobodies.
ジャーナル・号・ページ	Elife, Vol. 13, Year 2024
掲載日	2024年4月26日
著者	Christian Galicia / Giambattista Guaitoli / Marcus Fislage / Christian Johannes Gloeckner / Wim Versées /
PubMed 要旨	Roco proteins entered the limelight after mutations in human LRRK2 were identified as a major cause of familial Parkinson's disease. LRRK2 is a large and complex protein combining a GTPase and ...Roco proteins entered the limelight after mutations in human LRRK2 were identified as a major cause of familial Parkinson's disease. LRRK2 is a large and complex protein combining a GTPase and protein kinase activity, and disease mutations increase the kinase activity, while presumably decreasing the GTPase activity. Although a cross-communication between both catalytic activities has been suggested, the underlying mechanisms and the regulatory role of the GTPase domain remain unknown. Several structures of LRRK2 have been reported, but structures of Roco proteins in their activated GTP-bound state are lacking. Here, we use single-particle cryo-electron microscopy to solve the structure of a bacterial Roco protein (CtRoco) in its GTP-bound state, aided by two conformation-specific nanobodies: Nb and Nb. This structure presents CtRoco in an active monomeric state, featuring a very large GTP-induced conformational change using the LRR-Roc linker as a hinge. Furthermore, this structure shows how Nb and Nb collaborate to activate CtRoco in an allosteric way. Altogether, our data provide important new insights into the activation mechanism of Roco proteins, with relevance to LRRK2 regulation, and suggest new routes for the allosteric modulation of their GTPase activity.
リンク	Elife / PubMed:38666771 / PubMed Central
手法	EM (単粒子)
解像度	3.55 - 8.3 Å
構造データ	EMDB-18879: Roco protein from C. tepidum in the GTP state bound to an activating Nanobody 手法: EM (単粒子) / 解像度: 8.3 Å EMDB-18882: Roco protein from C. tepidum in the GTP state bound to the activating Nanobodies NbRoco1 and NbRoco2 手法: EM (単粒子) / 解像度: 7.66 Å 18884 8r4b EMDB-18884: Ensemble map of the Roco protein from C. tepidum in the GTP state bound to the activating Nanobodies NbRoco1 and NbRoco2 PDB-8r4b: Roco protein from C. tepidum in the GTP state bound to the activating Nanobodies NbRoco1 and NbRoco2 手法: EM (単粒子) / 解像度: 3.88 Å 18885 8r4c EMDB-18885: Focused map on the LRR domain of the Roco protein from C. tepidum bound to the activating Nanobody NbRoco2 PDB-8r4c: LRR domain of Roco protein from C. tepidum bound to the activating Nanobody NbRoco2 手法: EM (単粒子) / 解像度: 3.55 Å 18886 8r4d EMDB-18886, PDB-8r4d: Focused map on the Roc-COR domains of the Roco protein from C. tepidum in the GTP state bound to the activating Nanobody NbRoco1 手法: EM (単粒子) / 解像度: 3.88 Å
化合物	ChemComp-GSP: 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE / GTP-γ-S
由来	chlorobaculum tepidum (バクテリア) lama glama (ラマ)
キーワード	HYDROLASE (加水分解酵素) / GTPase (GTPアーゼ) / Nanobody (ナノボディ) / Parkinson's Disease (パーキンソン病) / Allostery activator