title: Structurally unique interaction of RBD-like and PH domains is crucial for yeast pheromone signaling.
abstract: The Ste5 protein forms a scaffold that associates and regulates the components of the mitogen-activated protein (MAP) kinase cascade that controls mating-pheromone-mediated signaling in the yeast Saccharomyces cerevisiae. Although it is known that the MEK kinase of the pathway, Ste11, associates with Ste5, details of this interaction have not been established. We identified a Ras-binding-domain-like (RBL) region in the Ste11 protein that is required specifically for the kinase to function in the mating pathway. This module is structurally related to domains in other proteins that mediate Ras-MAP kinase kinase kinase associations; however, this RBL module does not interact with Ras, but instead binds the PH domain of the Ste5 scaffold. Structural and functional studies suggest that the key role of this PH domain is to mediate the Ste5-Ste11 interaction. Overall these two evolutionarily conserved modules interact with each other through a unique interface, and thus in the pheromone pathway the structural context of the RBL domain contribution to kinase activation has been shifted through a change of its interaction partner from Ras to a PH domain.
authors.affiliation: Life Sciences, National Research Council, Montreal, QC, Canada.
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Yerko
authors.forename: Traian
authors.initials: T
authors.lastname: Sulea
authors.forename: Irena
authors.initials: I
authors.lastname: Ekiel
authors.forename: Doreen
authors.initials: D
authors.lastname: Harcus
authors.forename: Jason
authors.initials: J
authors.lastname: Baardsnes
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Cygler
authors.forename: Malcolm
authors.initials: M
authors.lastname: Whiteway
authors.forename: Cunle
authors.initials: C
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D001665:Binding Sites; D049770:Genes, Mating Type, Fungal; D020930:MAP Kinase Kinase Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010449:Peptide Mapping; D010675:Pheromones / Q000502:physiology*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010675:Pheromones; C080321:STE5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D020930:MAP Kinase Kinase Kinases; C067018:Ste11 protein, S cerevisiae