title: The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1.
abstract: The small G protein Rho has emerged as a key regulator of cellular events involving cytoskeletal reorganization. Here we report the 2.2 A crystal structure of RhoA bound to an effector domain of protein kinase PKN/PRK1. The structure reveals the antiparallel coiled-coil finger (ACC finger) fold of the effector domain that binds to the Rho specificity-determining regions containing switch I, beta strands B2 and B3, and the C-terminal alpha helix A5, predominantly by specific hydrogen bonds. The ACC finger fold is distinct from those for other small G proteins and provides evidence for the diverse ways of effector recognition. Sequence analysis based on the structure suggests that the ACC finger fold is widespread in Rho effector proteins.
authors.affiliation: Division of Structural Biology, Nara Institute of Science and Technology, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Maesaki
authors.forename: K
authors.initials: K
authors.lastname: Ihara
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: S
authors.initials: S
authors.lastname: Kuroda
authors.forename: K
authors.initials: K
authors.lastname: Kaibuchi
authors.forename: T
authors.initials: T
authors.lastname: Hakoshima
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D016350:Leucine Zippers; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D020742:rhoA GTP-Binding Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D016244:Guanosine 5'-O-(3-Thiotriphosphate); C061570:protein kinase N; D011493:Protein Kinase C; D020742:rhoA GTP-Binding Protein; D008274:Magnesium