Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling

• Autores: Rinaldi, J.; Wu, J.; Yang, J.; Ralston, C.Y.; Sankaran, B.; Moreno, S.; Taylor, S.S.
• Año de publicación: 2010
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Structure 2010;18(11):1471-1482
• Materia: cyclic AMP; fungal protein; protein bcy 1; protein pka; unclassified drug; article; nonhuman; phylogeny; priority journal; protein interaction; protein structure; Saccharomyces cerevisiae; signal transduction; yeast; Cluster Analysis; Crystallography; Cyclic AMP-Dependent Protein Kinases; Evolution, Molecular; Models, Molecular; Molecular Dynamics Simulation; Phylogeny; Protein Conformation; Protein Subunits; Regulatory Sequences, Nucleic Acid; Saccharomyces cerevisiae; Signal Transduction; Eukaryota; Fungi; Mammalia; Saccharomyces cerevisiae; Saccharomycotina
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

The major cAMP receptors in eukaryotes are the regulatory (R) subunits of PKA, an allosteric enzyme conserved in fungi through mammals. While mammals have four R-subunit genes, Saccharomyces cerevisiae has only one, Bcy1. To achieve a molecular understanding of PKA activation in yeast and to explore the evolution of cyclic-nucleotide binding (CNB) domains, we solved the structure of cAMP-bound Bcy1(168-416). Surprisingly, the relative orientation of the two CNB domains in Bcy1 is very different from mammalian R-subunits. This quaternary structure is defined primarily by a fungi-specific sequence in the hinge between the αB/αC helices of the CNB-A domain. The unique interface between the two CNB domains in Bcy1 defines the allosteric mechanism for cooperative activation of PKA by cAMP. Some interface motifs are isoform-specific while others, although conserved, play surprisingly different roles in each R-subunit. Phylogenetic analysis shows that structural differences in Bcy1 are shared by fungi of the subphylum Saccharomycotina. © 2010 Elsevier Ltd.
Fil:Rinaldi, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Moreno, S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.