6HLU

Crystal structure of the LRR-Roc-COR domain of the Chlorobium tepidum Roco protein

6HLU の概要

• エントリーDOI: 10.2210/pdb6hlu/pdb
• 分子名称: Rab family protein (1 entity in total)
• 機能のキーワード: gtpase, lrrk2, roco proteins, hydrolase
• 由来する生物種: Chlorobaculum tepidum (Chlorobium tepidum)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 219477.42

構造登録者

Deyaert, E.,Versees, W.,Singh, R. (登録日: 2018-09-11, 公開日: 2018-12-26, 最終更新日: 2024-01-24)

主引用文献

Deyaert, E.,Leemans, M.,Singh, R.K.,Gallardo, R.,Steyaert, J.,Kortholt, A.,Lauer, J.,Versees, W.
Structure and nucleotide-induced conformational dynamics of theChlorobium tepidumRoco protein.
Biochem. J., 476:51-66, 2019

PubMed Abstract: The LRR (leucine-rich repeat)-Roc (Ras of complex proteins)-COR (C-terminal of Roc) domains are central to the action of nearly all Roco proteins, including the Parkinson's disease-associated protein LRRK2 (leucine-rich repeat kinase 2). We previously demonstrated that the Roco protein from (CtRoco) undergoes a dimer-monomer cycle during the GTPase reaction, with the protein being mainly dimeric in the nucleotide-free and GDP (guanosine-5'-diphosphate)-bound states and monomeric in the GTP (guanosine-5'-triphosphate)-bound state. Here, we report a crystal structure of CtRoco in the nucleotide-free state showing for the first time the arrangement of the LRR-Roc-COR. This structure reveals a compact dimeric arrangement and shows an unanticipated intimate interaction between the Roc GTPase domains in the dimer interface, involving residues from the P-loop, the switch II loop, the G4 region and a loop which we named the 'Roc dimerization loop'. Hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) is subsequently used to highlight structural alterations induced by individual steps along the GTPase cycle. The structure and HDX-MS data propose a pathway linking nucleotide binding to monomerization and relaying the conformational changes via the Roc switch II to the LRR and COR domains. Together, this work provides important new insights in the regulation of the Roco proteins.

PubMed: 30538153
DOI: 10.1042/BCJ20180803

実験手法

X-RAY DIFFRACTION (3.29 Å)