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Abstract:

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.

Registro:

Documento: Artículo
Título:Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling
Autor:Rinaldi, J.; Wu, J.; Yang, J.; Ralston, C.Y.; Sankaran, B.; Moreno, S.; Taylor, S.S.
Filiación:Department of Biological Chemistry, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, 1428, Buenos Aires, Argentina
Department of Chemistry/Biochemistry and Pharmacology, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093-0654, United States
Berkeley Center for Structural Biology, Lawrence Berkeley Laboratory, 1 Cyclotron Road, BLDG 6R2100, Berkeley, CA 94720, United States
Palabras clave: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
Año:2010
Volumen:18
Número:11
Página de inicio:1471
Página de fin:1482
DOI: http://dx.doi.org/10.1016/j.str.2010.08.013
Título revista:Structure
Título revista abreviado:Structure
ISSN:09692126
CODEN:STRUE
CAS:cyclic AMP, 60-92-4; Cyclic AMP-Dependent Protein Kinases, 2.7.11.11; Protein Subunits
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_09692126_v18_n11_p1471_Rinaldi.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09692126_v18_n11_p1471_Rinaldi

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Citas:

---------- APA ----------
Rinaldi, J., Wu, J., Yang, J., Ralston, C.Y., Sankaran, B., Moreno, S. & Taylor, S.S. (2010) . Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling. Structure, 18(11), 1471-1482.
http://dx.doi.org/10.1016/j.str.2010.08.013
---------- CHICAGO ----------
Rinaldi, J., Wu, J., Yang, J., Ralston, C.Y., Sankaran, B., Moreno, S., et al. "Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling" . Structure 18, no. 11 (2010) : 1471-1482.
http://dx.doi.org/10.1016/j.str.2010.08.013
---------- MLA ----------
Rinaldi, J., Wu, J., Yang, J., Ralston, C.Y., Sankaran, B., Moreno, S., et al. "Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling" . Structure, vol. 18, no. 11, 2010, pp. 1471-1482.
http://dx.doi.org/10.1016/j.str.2010.08.013
---------- VANCOUVER ----------
Rinaldi, J., Wu, J., Yang, J., Ralston, C.Y., Sankaran, B., Moreno, S., et al. Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling. Structure. 2010;18(11):1471-1482.
http://dx.doi.org/10.1016/j.str.2010.08.013