3dpu
From Proteopedia
RocCOR domain tandem of Rab family protein (Roco)
Structural highlights
FunctionEvolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedRas of complex proteins (Roc) belongs to the superfamily of Ras-related small G-proteins that always occurs in tandem with the C-terminal of Roc (COR) domain. This Roc-COR tandem is found in the bacterial and eukaryotic world. Its most prominent member is the leucine-rich repeat kinase LRRK2, which is mutated and activated in Parkinson patients. Here, we investigated biochemically and structurally the Roco protein from Chlorobium tepidum. We show that Roc is highly homologous to Ras, whereas the COR domain is a dimerisation device. The juxtaposition of the G-domains and mutational analysis suggest that the Roc GTPase reaction is stimulated and/or regulated by dimerisation in a nucleotide-dependent manner. The region most conserved between bacteria and man is the interface between Roc and COR, where single-point Parkinson mutations of the Roc and COR domains are in close proximity. The analogous mutations in C. tepidum Roc-COR decrease the GTPase reaction rate, most likely due to a modification of the interaction between the Roc and COR domains. Structure of the Roc-COR domain tandem of C. tepidum, a prokaryotic homologue of the human LRRK2 Parkinson kinase.,Gotthardt K, Weyand M, Kortholt A, Van Haastert PJ, Wittinghofer A EMBO J. 2008 Aug 20;27(16):2239-49. Epub 2008 Jul 24. PMID:18650931[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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