PDBsum entry 2dfk

Cell cycle

PDB id: 2dfk

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.Schwarz, 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

Protein chains

Q9QX73  (ARHG9_RAT) -  Rho guanine nucleotide exchange factor 9 from Rattus norvegicus

Seq: 493 a.a.

Struc: 365 a.a.

Protein chains

P60953  (CDC42_HUMAN) -  Cell division control protein 42 homolog from Homo sapiens

Seq: 191 a.a.

Struc: 187 a.a.

Enzyme reactions

• Enzyme class: Chains B, D: E.C.3.6.5.2 - small monomeric GTPase.
• Reaction: GTP + H2O = GDP + phosphate + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

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.