title: Structure of Cdc42 bound to the GTPase binding domain of PAK.
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.
authors.affiliation: Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: A
authors.initials: A
authors.lastname: Morreale
authors.forename: M
authors.initials: M
authors.lastname: Venkatesan
authors.forename: H R
authors.initials: HR
authors.lastname: Mott
authors.forename: D
authors.initials: D
authors.lastname: Owen
authors.forename: D
authors.initials: D
authors.lastname: Nietlispach
authors.forename: P N
authors.initials: PN
authors.lastname: Lowe
authors.forename: E D
authors.initials: ED
authors.lastname: Laue
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence / Q000235:genetics; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012996:Solutions; D013379:Substrate Specificity; D051316:Wiskott-Aldrich Syndrome Protein; D020764:cdc42 GTP-Binding Protein / Q000737:chemistry* / Q000378:metabolism*; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D011506:Proteins; D012996:Solutions; D051316:Wiskott-Aldrich Syndrome Protein; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020558:GTP Phosphohydrolases; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins