3of1 | pdb_00003of1
Crystal Structure of Bcy1, the Yeast Regulatory Subunit of PKA
Structural highlights
FunctionKAPR_YEAST Regulatory subunit of the cyclic AMP-dependent protein kinase (PKA), an effector of the Ras/cAMP pathway. Inhibits PKA activity in the absence of cAMP. cAMP activates PKA and promotes growth and proliferation in response to good nutrient conditions. Together with ZDS1, provides a negative feedback control on the cell wall integrity-signaling pathway by acting as a negative regulator of MAP kinase SLT2/MPK1.[1] [2] [3] [4] Publication Abstract from PubMedThe 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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