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PDBsum entry 2dfk

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protein ligands Protein-protein interface(s) links
Cell cycle PDB id
2dfk
Jmol
Contents
Protein chains
365 a.a. *
187 a.a. *
Ligands
GOL ×6
SO4 ×2
Waters ×581
* Residue conservation analysis
PDB id:
2dfk
Name: Cell cycle
Title: Crystal structure of the cdc42-collybistin ii complex
Structure: Collybistin ii. Chain: a, c. Fragment: residues 10-411. Engineered: yes. Cell division cycle 42 isoform 1. Chain: b, d. Synonym: gtp-binding protein, 25kd. Cdc42. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Homo sapiens. Human. Organism_taxid: 9606.
Biol. unit: Tetramer (from PQS)
Resolution:
2.15Å     R-factor:   0.183     R-free:   0.229
Authors: S.Xiang,E.Y.Kim,J.J.Connelly,N.Nassar,J.Kirsch,J.Winking,G.S H.Schindelin
Key ref:
S.Xiang et al. (2006). The crystal structure of Cdc42 in complex with collybistin II, a gephyrin-interacting guanine nucleotide exchange factor. J Mol Biol, 359, 35-46. PubMed id: 16616186 DOI: 10.1016/j.jmb.2006.03.019
Date:
02-Mar-06     Release date:   02-May-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
No UniProt id for this chain
Struc: 365 a.a.
Protein chains
No UniProt id for this chain
Struc: 187 a.a.
Key:    Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   21 terms 
  Biological process     cardiac conduction system development   70 terms 
  Biochemical function     nucleotide binding     11 terms  

 

 
DOI no: 10.1016/j.jmb.2006.03.019 J Mol Biol 359:35-46 (2006)
PubMed id: 16616186  
 
 
The crystal structure of Cdc42 in complex with collybistin II, a gephyrin-interacting guanine nucleotide exchange factor.
S.Xiang, E.Y.Kim, J.J.Connelly, N.Nassar, J.Kirsch, J.Winking, G.Schwarz, H.Schindelin.
 
  ABSTRACT  
 
The synaptic localization of ion channel receptors is essential for efficient synaptic transmission and the precise regulation of diverse neuronal functions. In the central nervous system, ion channel receptors reside in the postsynaptic membrane where they are juxtaposed to presynaptic terminals. For proper function, these ion channels have to be anchored to the cytoskeleton, and in the case of the inhibitory glycine and gamma-amino-butyric acid type A (GABA(A)) receptors this interaction is mediated by a gephyrin centered scaffold. Highlighting its central role in this receptor anchoring scaffold, gephyrin interacts with a number of proteins, including the neurospecific guanine nucleotide exchange factor collybistin. Collybistin belongs to the Dbl family of guanine nucleotide exchange factors, occurs in multiple splice variants, and is specific for Cdc42, a small GTPase belonging to the Rho family. The 2.3 Angstroms resolution crystal structure of the Cdc42-collybistin II complex reveals a novel conformation of the switch I region of Cdc42. It also provides the first direct observation of structural changes in the relative orientation of the Dbl-homology domain and the pleckstrin-homology domain in the same Dbl family protein. Biochemical data indicate that gephyrin negatively regulates collybistin activity.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. Structural changes of the PH domain. (a) Structural comparison of the tandem DH/PH domains. Collybistin II, Tiam 1, Dbs, intersectin and Sos1 were aligned according to the conserved regions of their DH domains. In collybistin II, the PH domains are colored green in the open conformation and gray in the closed conformation. (b) Collybistin II in the open conformation. Residues that lose solvent-accessible surface area upon transition to the closed conformation are highlighted with positively charged residues in blue, negatively charged residues in red, polar residues in cyan and non-polar residues in gray. (c) Collybistin II in the closed conformation (same color code). An additional salt-bridge between Asp136 (red) and Lys379 (blue) in the closed conformation is visible on the bottom of the DH/PH domain interface. (b) and (c) are aligned according to their PH domains. Residues highlighted in (b) with an arrow are disordered in the open conformation.
Figure 5.
Figure 5. Membrane interaction model of the Cdc42-collybistin II complex. (a) The electrostatic potential of the open conformation of the Cdc42-collybistin II complex, calculated at zero ionic strength and contoured at 1.5 kT (blue) and -1.5 kT (red). (b) Model of the interaction between the plasma membrane and the complex in the open conformation. The observed conformation of the Cdc42 C terminus is colored in cyan, whereas the physiologically relevant conformations present in the Cdc42-Dbs and Cdc42-GDI complexes are colored in gray and red, respectively.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 359, 35-46) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20345913 S.Reddy-Alla, B.Schmitt, J.Birkenfeld, V.Eulenburg, S.Dutertre, C.Böhringer, M.Götz, H.Betz, and T.Papadopoulos (2010).
PH-domain-driven targeting of collybistin but not Cdc42 activation is required for synaptic gephyrin clustering.
  Eur J Neurosci, 31, 1173-1184.  
18615734 V.M.Kalscheuer, L.Musante, C.Fang, K.Hoffmann, C.Fuchs, E.Carta, E.Deas, K.Venkateswarlu, C.Menzel, R.Ullmann, N.Tommerup, L.Dalprà, A.Tzschach, A.Selicorni, B.Lüscher, H.H.Ropers, K.Harvey, and R.J.Harvey (2009).
A balanced chromosomal translocation disrupting ARHGEF9 is associated with epilepsy, anxiety, aggression, and mental retardation.
  Hum Mutat, 30, 61-68.  
18707791 R.J.Harvey, M.Topf, K.Harvey, and M.I.Rees (2008).
The genetics of hyperekplexia: more than startle!
  Trends Genet, 24, 439-447.  
18625319 T.Papadopoulos, V.Eulenburg, S.Reddy-Alla, I.M.Mansuy, Y.Li, and H.Betz (2008).
Collybistin is required for both the formation and maintenance of GABAergic postsynapses in the hippocampus.
  Mol Cell Neurosci, 39, 161-169.  
17190834 K.Murayama, M.Shirouzu, Y.Kawasaki, M.Kato-Murayama, K.Hanawa-Suetsugu, A.Sakamoto, Y.Katsura, A.Suenaga, M.Toyama, T.Terada, M.Taiji, T.Akiyama, and S.Yokoyama (2007).
Crystal structure of the rac activator, Asef, reveals its autoinhibitory mechanism.
  J Biol Chem, 282, 4238-4242.
PDB code: 2dx1
17145773 M.J.Hamann, C.M.Lubking, D.N.Luchini, and D.D.Billadeau (2007).
Asef2 functions as a Cdc42 exchange factor and is stimulated by the release of an autoinhibitory module from a concealed C-terminal activation element.
  Mol Cell Biol, 27, 1380-1393.  
17391702 M.K.Chhatriwala, L.Betts, D.K.Worthylake, and J.Sondek (2007).
The DH and PH domains of Trio coordinately engage Rho GTPases for their efficient activation.
  J Mol Biol, 368, 1307-1320.
PDB code: 2nz8
17704816 N.Mitin, L.Betts, M.E.Yohe, C.J.Der, J.Sondek, and K.L.Rossman (2007).
Release of autoinhibition of ASEF by APC leads to CDC42 activation and tumor suppression.
  Nat Struct Mol Biol, 14, 814-823.
PDB code: 2pz1
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.