3of1

Publication Abstract from PubMed

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 alphaB/alphaC 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.

Structure of yeast regulatory subunit: a glimpse into the evolution of PKA signaling.,Rinaldi J, Wu J, Yang J, Ralston CY, Sankaran B, Moreno S, Taylor SS Structure. 2010 Nov 10;18(11):1471-82. PMID:21070946^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.