PDBsum entry: 1e0a

Signalling protein

PDB id: 1e0a

Contents

Protein chains

184 a.a. *

46 a.a. *

Ligands

GNP

Metals

_MG

Waters ×6

* Residue conservation analysis

PDB id:

1e0a

Name:

Signalling protein

Title:

Cdc42 complexed with the gtpase binding domain of p21 activated kinase

Structure:

G25k gtp-binding protein, placental isoform (gp), cdc42 homolog. Chain: a. Fragment: 1-184. Engineered: yes. Mutation: yes. Other_details: complexed with 5'-guanosyl-imido-triphosphate. Serine/threonine-protein kinase pak-alpha.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_variant: de3. Rattus norvegicus. Norway rat.

NMR struc:

20 models

Authors:

A.Morreale,M.Venkatesan,H.R.Mott,D.Owen,D.Nietlispach, P.N.Lowe,E.D.Laue

Key ref:

A.Morreale et al. (2000). Structure of Cdc42 bound to the GTPase binding domain of PAK. Nat Struct Biol, 7, 384-388. PubMed id: 10802735 DOI: 10.1038/75158

Date:

16-Mar-00 Release date: 18-Apr-00

Protein chain

P60953  (CDC42_HUMAN) -  Cell division control protein 42 homolog

Seq: 191 a.a.

Struc: 184 a.a.*

Protein chain

P35465  (PAK1_RAT) -  Serine/threonine-protein kinase PAK 1

Seq: 544 a.a.

Struc: 46 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain B: E.C.2.7.11.1 - Non-specific serine/threonine protein kinase.
• Reaction: ATP + a protein = ADP + a phosphoprotein

ATP + protein = ADP (Bound ligand (Het Group name = GNP) matches with 78.00% similarity) + phosphoprotein

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

 Gene Ontology (GO) functional annotation 

• Cellular component: mitotic spindle (12 terms)
• Biological process: positive regulation of cell cycle cytokinesis (20 terms)
• Biochemical function: nucleotide binding (5 terms)

reference

DOI no: 10.1038/75158

Nat Struct Biol 7:384-388 (2000)

PubMed id: 10802735

Structure of Cdc42 bound to the GTPase binding domain of PAK.

A.Morreale, M.Venkatesan, H.R.Mott, D.Owen, D.Nietlispach, P.N.Lowe, E.D.Laue.

ABSTRACT

The Rho family GTPases, Cdc42, Rac and Rho, regulate signal transduction pathways via interactions with downstream effector proteins. We report here the solution structure of Cdc42 bound to the GTPase binding domain of alphaPAK, an effector of both Cdc42 and Rac. The structure is compared with those of Cdc42 bound to similar fragments of ACK and WASP, two effector proteins that bind only to Cdc42. The N-termini of all three effector fragments bind in an extended conformation to strand beta2 of Cdc42, and contact helices alpha1 and alpha5. The remaining residues bind to switches I and II of Cdc42, but in a significantly different manner. The structure, together with mutagenesis data, suggests reasons for the specificity of these interactions and provides insight into the mechanism of PAK activation.

Selected figure(s)

Figure 1.
Figure 1. Sequence comparisons. a, Comparison of the Cdc42 binding domains of PAK, ACK and WASP. The secondary structures adopted by the fragments on binding to Cdc42 are shown. b, Comparison of Cdc42 and Rac1. Nonconserved residues involved in PAK interactions are boxed. The residues comprising switch regions I and II are indicated by black lines and the secondary structure of Cdc42 is shown. In both (a) and (b) conserved residues involved in the Cdc42 -PAK interaction are yellow (hydrophobic), green (Asp, Gln, Ser and Thr), red (acidic), magenta (His) and dark blue (basic). This figure was produced using the program Alscript30.

Figure 2.
Figure 2. Structure of free and bound PAK. a, Summary of the NMR data for free PAK(75 -118). Sequential and short range NOEs are indicated along the sequence of PAK(75 -118). NOEs are shown as filled rectangular bars, with the height of the bars reflecting the relative strength of the NOE. Circles in the panel indicate NH protons that do not exchange with the solvent. Squares indicate 3J[HNH ]coupling constants of <6 Hz. b,c, Structure of the Cdc42 -PAK complex. Residues 1 -180 of Cdc42 and residues 75 -108 of PAK are shown. Cdc42 is blue and PAK is yellow. A stereo view of the backbone (C trace) of the 20 lowest energy structures (out of 100 calculated) is shown in (b) and a representation of the structure closest to the mean is shown in (c). In (c), residues at the ends of secondary structure elements that are involved in the interaction are labeled in green (PAK) and red (Cdc42). This figure and Figs 3, 4 were produced using the programs MOLSCRIPT31 and Raster 3D^32.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 384-388) copyright 2000.

Figures were selected by the author.