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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2015
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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. |
format | Online Article Text |
id | pubmed-4475381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
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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