PDBsum entry 3dpu

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protein Protein-protein interface(s) links
Signaling protein PDB id
Protein chains
485 a.a. *
328 a.a. *
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Roccor domain tandem of rab family protein (roco)
Structure: Rab family protein. Chain: a, b. Fragment: roccor, unp residues 412-946. Engineered: yes. Mutation: yes
Source: Chlorobaculum tepidum. Organism_taxid: 1097. Strain: chlorobium tepidum tls. Gene: ct1526. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.90Å     R-factor:   0.232     R-free:   0.270
Authors: K.Gotthardt,M.Weyand,A.Kortholt,P.J.M.Van Haastert,A.Witting
Key ref: K.Gotthardt et al. (2008). Structure of the Roc-COR domain tandem of C. tepidum, a prokaryotic homologue of the human LRRK2 Parkinson kinase. EMBO J, 27, 2239-2249. PubMed id: 18650931
09-Jul-08     Release date:   12-Aug-08    
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Protein chain
Pfam   ArchSchema ?
Q8KC98  (Q8KC98_CHLTE) -  Rab family protein
1102 a.a.
485 a.a.*
Protein chain
Pfam   ArchSchema ?
Q8KC98  (Q8KC98_CHLTE) -  Rab family protein
1102 a.a.
328 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 28 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   1 term 
  Biological process     small GTPase mediated signal transduction   1 term 
  Biochemical function     GTP binding     1 term  


EMBO J 27:2239-2249 (2008)
PubMed id: 18650931  
Structure of the Roc-COR domain tandem of C. tepidum, a prokaryotic homologue of the human LRRK2 Parkinson kinase.
K.Gotthardt, M.Weyand, A.Kortholt, P.J.Van Haastert, A.Wittinghofer.
Ras 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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21220305 K.Domanska, S.Vanderhaegen, V.Srinivasan, E.Pardon, F.Dupeux, J.A.Marquez, S.Giorgetti, M.Stoppini, L.Wyns, V.Bellotti, and J.Steyaert (2011).
Atomic structure of a nanobody-trapped domain-swapped dimer of an amyloidogenic beta2-microglobulin variant.
  Proc Natl Acad Sci U S A, 108, 1314-1319.
PDB code: 2x89
21073465 V.Daniëls, R.Vancraenenbroeck, B.M.Law, E.Greggio, E.Lobbestael, F.Gao, M.De Maeyer, M.R.Cookson, K.Harvey, V.Baekelandt, and J.M.Taymans (2011).
Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant.
  J Neurochem, 116, 304-315.  
  21276267 W.Thys, S.De Houwer, J.Demeulemeester, O.Taltynov, R.Vancraenenbroeck, M.Gérard, J.De Rijck, R.Gijsbers, F.Christ, and Z.Debyser (2011).
Interplay between HIV Entry and Transportin-SR2 Dependency.
  Retrovirology, 8, 7.  
20173330 C.H.Hsu, D.Chan, and B.Wolozin (2010).
LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins.
  Neurodegener Dis, 7, 68-75.  
21048939 K.Haebig, C.J.Gloeckner, M.G.Miralles, F.Gillardon, C.Schulte, O.Riess, M.Ueffing, S.Biskup, and M.Bonin (2010).
ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2.
  PLoS One, 5, e13762.  
19712061 C.L.Klein, G.Rovelli, W.Springer, C.Schall, T.Gasser, and P.J.Kahle (2009).
Homo- and heterodimerization of ROCO kinases: LRRK2 kinase inhibition by the LRRK2 ROCO fragment.
  J Neurochem, 111, 703-715.  
19733152 E.Greggio, J.M.Taymans, E.Y.Zhen, J.Ryder, R.Vancraenenbroeck, A.Beilina, P.Sun, J.Deng, H.Jaffe, V.Baekelandt, K.Merchant, and M.R.Cookson (2009).
The Parkinson's disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites.
  Biochem Biophys Res Commun, 389, 449-454.  
  19570025 E.Greggio, and M.R.Cookson (2009).
Leucine-rich repeat kinase 2 mutations and Parkinson's disease: three questions.
  ASN Neuro, 1, 0.  
19424291 R.Gasper, S.Meyer, K.Gotthardt, M.Sirajuddin, and A.Wittinghofer (2009).
It takes two to tango: regulation of G proteins by dimerization.
  Nat Rev Mol Cell Biol, 10, 423-429.  
19625296 R.M.Sancho, B.M.Law, and K.Harvey (2009).
Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways.
  Hum Mol Genet, 18, 3955-3968.  
19806182 S.Meyer, S.Böhme, A.Krüger, H.J.Steinhoff, J.P.Klare, and A.Wittinghofer (2009).
Kissing G domains of MnmE monitored by X-ray crystallography and pulse electron paramagnetic resonance spectroscopy.
  PLoS Biol, 7, e1000212.
PDB codes: 3gee 3geh 3gei
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