Cargando…
Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus
WalKR (YycFG) is the only essential two-component regulator in the human pathogen Staphylococcus aureus. WalKR regulates peptidoglycan synthesis, but this function alone does not explain its essentiality. Here, to further understand WalKR function, we investigate a suppressor mutant that arose when...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624279/ https://www.ncbi.nlm.nih.gov/pubmed/31296851 http://dx.doi.org/10.1038/s41467-019-10932-4 |
_version_ | 1783434237552099328 |
---|---|
author | Monk, Ian R. Shaikh, Nausad Begg, Stephanie L. Gajdiss, Mike Sharkey, Liam K. R. Lee, Jean Y. H. Pidot, Sacha J. Seemann, Torsten Kuiper, Michael Winnen, Brit Hvorup, Rikki Collins, Brett M. Bierbaum, Gabriele Udagedara, Saumya R. Morey, Jacqueline R. Pulyani, Neha Howden, Benjamin P. Maher, Megan J. McDevitt, Christopher A. King, Glenn F. Stinear, Timothy P. |
author_facet | Monk, Ian R. Shaikh, Nausad Begg, Stephanie L. Gajdiss, Mike Sharkey, Liam K. R. Lee, Jean Y. H. Pidot, Sacha J. Seemann, Torsten Kuiper, Michael Winnen, Brit Hvorup, Rikki Collins, Brett M. Bierbaum, Gabriele Udagedara, Saumya R. Morey, Jacqueline R. Pulyani, Neha Howden, Benjamin P. Maher, Megan J. McDevitt, Christopher A. King, Glenn F. Stinear, Timothy P. |
author_sort | Monk, Ian R. |
collection | PubMed |
description | WalKR (YycFG) is the only essential two-component regulator in the human pathogen Staphylococcus aureus. WalKR regulates peptidoglycan synthesis, but this function alone does not explain its essentiality. Here, to further understand WalKR function, we investigate a suppressor mutant that arose when WalKR activity was impaired; a histidine to tyrosine substitution (H271Y) in the cytoplasmic Per-Arnt-Sim (PAS(CYT)) domain of the histidine kinase WalK. Introducing the WalK(H271Y) mutation into wild-type S. aureus activates the WalKR regulon. Structural analyses of the WalK PAS(CYT) domain reveal a metal-binding site, in which a zinc ion (Zn(2+)) is tetrahedrally-coordinated by four amino acids including H271. The WalK(H271Y) mutation abrogates metal binding, increasing WalK kinase activity and WalR phosphorylation. Thus, Zn(2+)-binding negatively regulates WalKR. Promoter-reporter experiments using S. aureus confirm Zn(2+) sensing by this system. Identification of a metal ligand recognized by the WalKR system broadens our understanding of this critical S. aureus regulon. |
format | Online Article Text |
id | pubmed-6624279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66242792019-07-15 Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus Monk, Ian R. Shaikh, Nausad Begg, Stephanie L. Gajdiss, Mike Sharkey, Liam K. R. Lee, Jean Y. H. Pidot, Sacha J. Seemann, Torsten Kuiper, Michael Winnen, Brit Hvorup, Rikki Collins, Brett M. Bierbaum, Gabriele Udagedara, Saumya R. Morey, Jacqueline R. Pulyani, Neha Howden, Benjamin P. Maher, Megan J. McDevitt, Christopher A. King, Glenn F. Stinear, Timothy P. Nat Commun Article WalKR (YycFG) is the only essential two-component regulator in the human pathogen Staphylococcus aureus. WalKR regulates peptidoglycan synthesis, but this function alone does not explain its essentiality. Here, to further understand WalKR function, we investigate a suppressor mutant that arose when WalKR activity was impaired; a histidine to tyrosine substitution (H271Y) in the cytoplasmic Per-Arnt-Sim (PAS(CYT)) domain of the histidine kinase WalK. Introducing the WalK(H271Y) mutation into wild-type S. aureus activates the WalKR regulon. Structural analyses of the WalK PAS(CYT) domain reveal a metal-binding site, in which a zinc ion (Zn(2+)) is tetrahedrally-coordinated by four amino acids including H271. The WalK(H271Y) mutation abrogates metal binding, increasing WalK kinase activity and WalR phosphorylation. Thus, Zn(2+)-binding negatively regulates WalKR. Promoter-reporter experiments using S. aureus confirm Zn(2+) sensing by this system. Identification of a metal ligand recognized by the WalKR system broadens our understanding of this critical S. aureus regulon. Nature Publishing Group UK 2019-07-11 /pmc/articles/PMC6624279/ /pubmed/31296851 http://dx.doi.org/10.1038/s41467-019-10932-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Monk, Ian R. Shaikh, Nausad Begg, Stephanie L. Gajdiss, Mike Sharkey, Liam K. R. Lee, Jean Y. H. Pidot, Sacha J. Seemann, Torsten Kuiper, Michael Winnen, Brit Hvorup, Rikki Collins, Brett M. Bierbaum, Gabriele Udagedara, Saumya R. Morey, Jacqueline R. Pulyani, Neha Howden, Benjamin P. Maher, Megan J. McDevitt, Christopher A. King, Glenn F. Stinear, Timothy P. Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus |
title | Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus |
title_full | Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus |
title_fullStr | Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus |
title_full_unstemmed | Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus |
title_short | Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus |
title_sort | zinc-binding to the cytoplasmic pas domain regulates the essential walk histidine kinase of staphylococcus aureus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624279/ https://www.ncbi.nlm.nih.gov/pubmed/31296851 http://dx.doi.org/10.1038/s41467-019-10932-4 |
work_keys_str_mv | AT monkianr zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT shaikhnausad zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT beggstephaniel zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT gajdissmike zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT sharkeyliamkr zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT leejeanyh zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT pidotsachaj zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT seemanntorsten zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT kuipermichael zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT winnenbrit zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT hvoruprikki zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT collinsbrettm zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT bierbaumgabriele zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT udagedarasaumyar zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT moreyjacqueliner zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT pulyanineha zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT howdenbenjaminp zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT mahermeganj zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT mcdevittchristophera zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT kingglennf zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus AT stineartimothyp zincbindingtothecytoplasmicpasdomainregulatestheessentialwalkhistidinekinaseofstaphylococcusaureus |