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

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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...

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Detalles Bibliográficos
Autores principales: Rinaldi, J., Wu, J., Yang, J., Ralston, C.Y., Sankaran, B., Moreno, S., Taylor, S.S.
Formato: JOUR
Materias:
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
Signal Transduction
Eukaryota
Fungi
Mammalia
Saccharomycotina
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_09692126_v18_n11_p1471_Rinaldi
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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.

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