Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling
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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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_09692126_v18_n11_p1471_Rinaldi |
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paperaa:paper_09692126_v18_n11_p1471_Rinaldi2023-06-12T16:48:48Z Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling Structure 2010;18(11):1471-1482 Rinaldi, J. Wu, J. Yang, J. Ralston, C.Y. Sankaran, B. Moreno, S. Taylor, S.S. 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 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. 2010 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09692126_v18_n11_p1471_Rinaldi |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| language |
Inglés |
| orig_language_str_mv |
eng |
| topic |
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 |
| spellingShingle |
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 Rinaldi, J. Wu, J. Yang, J. Ralston, C.Y. Sankaran, B. Moreno, S. Taylor, S.S. Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling |
| topic_facet |
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 |
| description |
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. |
| format |
Artículo Artículo publishedVersion |
| author |
Rinaldi, J. Wu, J. Yang, J. Ralston, C.Y. Sankaran, B. Moreno, S. Taylor, S.S. |
| author_facet |
Rinaldi, J. Wu, J. Yang, J. Ralston, C.Y. Sankaran, B. Moreno, S. Taylor, S.S. |
| author_sort |
Rinaldi, J. |
| title |
Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling |
| title_short |
Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling |
| title_full |
Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling |
| title_fullStr |
Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling |
| title_full_unstemmed |
Structure of Yeast Regulatory Subunit: A Glimpse into the Evolution of PKA Signaling |
| title_sort |
structure of yeast regulatory subunit: a glimpse into the evolution of pka signaling |
| publishDate |
2010 |
| url |
http://hdl.handle.net/20.500.12110/paper_09692126_v18_n11_p1471_Rinaldi |
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