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Conformational coupling in the chemotaxis response regulator CheY

CheY, a response regulator protein in bacterial chemotaxis, serves as a prototype for the analysis of response regulator function in two-component signal transduction. Phosphorylation of a conserved aspartate at the active site mediates a conformational change at a distal signaling surface that modu...

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Autori principali: Schuster, Martin, Silversmith, Ruth E., Bourret, Robert B.
Natura: Articolo
Lingua:en
Pubblicazione: The National Academy of Sciences 2001
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Accesso online:https://ncbi.nlm.nih.gov/pmc/articles/PMC33503/
https://ncbi.nlm.nih.gov/pubmed/11353835
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1073/pnas.101571298
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spelling pubmed-335032001-06-26 Conformational coupling in the chemotaxis response regulator CheY Schuster, Martin Silversmith, Ruth E. Bourret, Robert B. Proc Natl Acad Sci U S A Biological Sciences CheY, a response regulator protein in bacterial chemotaxis, serves as a prototype for the analysis of response regulator function in two-component signal transduction. Phosphorylation of a conserved aspartate at the active site mediates a conformational change at a distal signaling surface that modulates interactions with the flagellar motor component FliM, the sensor kinase CheA, and the phosphatase CheZ. The objective of this study was to probe the conformational coupling between the phosphorylation site and the signaling surface of CheY in the reverse direction by quantifying phosphorylation activity in the presence and absence of peptides of CheA, CheZ, and FliM that specifically interact with CheY. Binding of these peptides dramatically impacted autophosphorylation of CheY by small molecule phosphodonors, which is indicative of reverse signal propagation in CheY. Autodephosphorylation and substrate affinity, however, were not significantly affected. Kinetic characterization of several CheY mutants suggested that conserved residues Thr-87, Tyr-106, and Lys-109, implicated in the activation mechanism, are not essential for conformational coupling. These findings provide structural and conceptual insights into the mechanism of CheY activation. Our results are consistent with a multistate thermodynamic model of response regulator activation. The National Academy of Sciences 2001-05-22 2001-05-15 /pmc/articles/PMC33503/ /pubmed/11353835 http://dx.doi.org/10.1073/pnas.101571298 Text en Copyright © 2001, The National Academy of Sciences
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Biological Sciences
spellingShingle Biological Sciences
Schuster, Martin
Silversmith, Ruth E.
Bourret, Robert B.
Conformational coupling in the chemotaxis response regulator CheY
description CheY, a response regulator protein in bacterial chemotaxis, serves as a prototype for the analysis of response regulator function in two-component signal transduction. Phosphorylation of a conserved aspartate at the active site mediates a conformational change at a distal signaling surface that modulates interactions with the flagellar motor component FliM, the sensor kinase CheA, and the phosphatase CheZ. The objective of this study was to probe the conformational coupling between the phosphorylation site and the signaling surface of CheY in the reverse direction by quantifying phosphorylation activity in the presence and absence of peptides of CheA, CheZ, and FliM that specifically interact with CheY. Binding of these peptides dramatically impacted autophosphorylation of CheY by small molecule phosphodonors, which is indicative of reverse signal propagation in CheY. Autodephosphorylation and substrate affinity, however, were not significantly affected. Kinetic characterization of several CheY mutants suggested that conserved residues Thr-87, Tyr-106, and Lys-109, implicated in the activation mechanism, are not essential for conformational coupling. These findings provide structural and conceptual insights into the mechanism of CheY activation. Our results are consistent with a multistate thermodynamic model of response regulator activation.
author Schuster, Martin
Silversmith, Ruth E.
Bourret, Robert B.
author_facet Schuster, Martin
Silversmith, Ruth E.
Bourret, Robert B.
author_sort Schuster, Martin
title Conformational coupling in the chemotaxis response regulator CheY
title_short Conformational coupling in the chemotaxis response regulator CheY
title_full Conformational coupling in the chemotaxis response regulator CheY
title_fullStr Conformational coupling in the chemotaxis response regulator CheY
title_full_unstemmed Conformational coupling in the chemotaxis response regulator CheY
title_sort conformational coupling in the chemotaxis response regulator chey
publisher The National Academy of Sciences
publisher_facet The National Academy of Sciences
publishDate 2001
url https://ncbi.nlm.nih.gov/pmc/articles/PMC33503/
https://ncbi.nlm.nih.gov/pubmed/11353835
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1073/pnas.101571298
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