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Molecular basis for the recognition of cyclic-di-AMP by PstA, a P(II)-like signal transduction protein

Cyclic-di-AMP (c-di-AMP) is a broadly conserved bacterial second messenger that is of importance in bacterial physiology. The molecular receptors mediating the cellular responses to the c-di-AMP signal are just beginning to be discovered. PstA is a previously uncharacterized P(II)-like protein which...

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Autores principales: Choi, Philip H, Sureka, Kamakshi, Woodward, Joshua J, Tong, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475381/
https://www.ncbi.nlm.nih.gov/pubmed/25693966
http://dx.doi.org/10.1002/mbo3.243
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author Choi, Philip H
Sureka, Kamakshi
Woodward, Joshua J
Tong, Liang
author_facet Choi, Philip H
Sureka, Kamakshi
Woodward, Joshua J
Tong, Liang
author_sort Choi, Philip H
collection PubMed
description Cyclic-di-AMP (c-di-AMP) is a broadly conserved bacterial second messenger that is of importance in bacterial physiology. The molecular receptors mediating the cellular responses to the c-di-AMP signal are just beginning to be discovered. PstA is a previously uncharacterized P(II)-like protein which has been identified as a c-di-AMP receptor. PstA is widely distributed and conserved among Gram-positive bacteria in the phylum Firmicutes. Here, we report the biochemical, structural, and functional characterization of PstA from Listeria monocytogenes. We have determined the crystal structures of PstA in the c-di-AMP-bound and apo forms at 1.6 and 2.9 Å resolution, respectively, which provide the molecular basis for its specific recognition of c-di-AMP. PstA forms a homotrimer structure that has overall similarity to the P(II) protein family which binds ATP. However, PstA is markedly different from P(II) proteins in the loop regions, and these structural differences mediate the specific recognition of their respective nucleotide ligand. The residues composing the c-di-AMP binding pocket are conserved, suggesting that c-di-AMP recognition by PstA is of functional importance. Disruption of pstA in L. monocytogenes affected c-di-AMP-mediated alterations in bacterial growth and lysis. Overall, we have defined the PstA family as a conserved and specific c-di-AMP receptor in bacteria.
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spelling pubmed-44753812015-06-26 Molecular basis for the recognition of cyclic-di-AMP by PstA, a P(II)-like signal transduction protein Choi, Philip H Sureka, Kamakshi Woodward, Joshua J Tong, Liang Microbiologyopen Original Research Cyclic-di-AMP (c-di-AMP) is a broadly conserved bacterial second messenger that is of importance in bacterial physiology. The molecular receptors mediating the cellular responses to the c-di-AMP signal are just beginning to be discovered. PstA is a previously uncharacterized P(II)-like protein which has been identified as a c-di-AMP receptor. PstA is widely distributed and conserved among Gram-positive bacteria in the phylum Firmicutes. Here, we report the biochemical, structural, and functional characterization of PstA from Listeria monocytogenes. We have determined the crystal structures of PstA in the c-di-AMP-bound and apo forms at 1.6 and 2.9 Å resolution, respectively, which provide the molecular basis for its specific recognition of c-di-AMP. PstA forms a homotrimer structure that has overall similarity to the P(II) protein family which binds ATP. However, PstA is markedly different from P(II) proteins in the loop regions, and these structural differences mediate the specific recognition of their respective nucleotide ligand. The residues composing the c-di-AMP binding pocket are conserved, suggesting that c-di-AMP recognition by PstA is of functional importance. Disruption of pstA in L. monocytogenes affected c-di-AMP-mediated alterations in bacterial growth and lysis. Overall, we have defined the PstA family as a conserved and specific c-di-AMP receptor in bacteria. BlackWell Publishing Ltd 2015-06 2015-02-18 /pmc/articles/PMC4475381/ /pubmed/25693966 http://dx.doi.org/10.1002/mbo3.243 Text en © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Choi, Philip H
Sureka, Kamakshi
Woodward, Joshua J
Tong, Liang
Molecular basis for the recognition of cyclic-di-AMP by PstA, a P(II)-like signal transduction protein
title Molecular basis for the recognition of cyclic-di-AMP by PstA, a P(II)-like signal transduction protein
title_full Molecular basis for the recognition of cyclic-di-AMP by PstA, a P(II)-like signal transduction protein
title_fullStr Molecular basis for the recognition of cyclic-di-AMP by PstA, a P(II)-like signal transduction protein
title_full_unstemmed Molecular basis for the recognition of cyclic-di-AMP by PstA, a P(II)-like signal transduction protein
title_short Molecular basis for the recognition of cyclic-di-AMP by PstA, a P(II)-like signal transduction protein
title_sort molecular basis for the recognition of cyclic-di-amp by psta, a p(ii)-like signal transduction protein
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475381/
https://www.ncbi.nlm.nih.gov/pubmed/25693966
http://dx.doi.org/10.1002/mbo3.243
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