Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate

Abstract It is recently appreciated that many bacterial chemoreceptors have ligand-binding domains (LBD) of the dCACHE family, a structure with two PAS-like subdomains, one membrane-proximal and the other membrane-distal. Previous studies had implicated only the membrane-distal subdomain in ligand r...

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Autores principales:	Mayra A. Machuca, Kevin S. Johnson, Yu C. Liu, David L. Steer, Karen M. Ottemann, Anna Roujeinikova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70d3bd8e624444ddaa9c81528f895161
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spelling	oai:doaj.org-article:70d3bd8e624444ddaa9c81528f8951612021-12-02T15:05:27ZHelicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate10.1038/s41598-017-14372-22045-2322https://doaj.org/article/70d3bd8e624444ddaa9c81528f8951612017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-14372-2https://doaj.org/toc/2045-2322Abstract It is recently appreciated that many bacterial chemoreceptors have ligand-binding domains (LBD) of the dCACHE family, a structure with two PAS-like subdomains, one membrane-proximal and the other membrane-distal. Previous studies had implicated only the membrane-distal subdomain in ligand recognition. Here, we report the 2.2 Å resolution crystal structure of dCACHE LBD of the Helicobacter pylori chemoreceptor TlpC. H. pylori tlpC mutants are outcompeted by wild type during stomach colonisation, but no ligands had been mapped to this receptor. The TlpC dCACHE LBD has two PAS-like subdomains, as predicted. The membrane-distal one possesses a long groove instead of a small, well-defined pocket. The membrane-proximal subdomain, in contrast, had a well-delineated pocket with a small molecule that we identified as lactate. We confirmed that amino acid residues making contact with the ligand in the crystal structure—N213, I218 and Y285 and Y249—were required for lactate binding. We determined that lactate is an H. pylori chemoattractant that is sensed via TlpC with a K D = 155 µM. Lactate is utilised by H. pylori, and our work suggests that this pathogen seeks out lactate using chemotaxis. Furthermore, our work suggests that dCACHE domain proteins can utilise both subdomains for ligand recognition.Mayra A. MachucaKevin S. JohnsonYu C. LiuDavid L. SteerKaren M. OttemannAnna RoujeinikovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mayra A. Machuca Kevin S. Johnson Yu C. Liu David L. Steer Karen M. Ottemann Anna Roujeinikova Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate
description	Abstract It is recently appreciated that many bacterial chemoreceptors have ligand-binding domains (LBD) of the dCACHE family, a structure with two PAS-like subdomains, one membrane-proximal and the other membrane-distal. Previous studies had implicated only the membrane-distal subdomain in ligand recognition. Here, we report the 2.2 Å resolution crystal structure of dCACHE LBD of the Helicobacter pylori chemoreceptor TlpC. H. pylori tlpC mutants are outcompeted by wild type during stomach colonisation, but no ligands had been mapped to this receptor. The TlpC dCACHE LBD has two PAS-like subdomains, as predicted. The membrane-distal one possesses a long groove instead of a small, well-defined pocket. The membrane-proximal subdomain, in contrast, had a well-delineated pocket with a small molecule that we identified as lactate. We confirmed that amino acid residues making contact with the ligand in the crystal structure—N213, I218 and Y285 and Y249—were required for lactate binding. We determined that lactate is an H. pylori chemoattractant that is sensed via TlpC with a K D = 155 µM. Lactate is utilised by H. pylori, and our work suggests that this pathogen seeks out lactate using chemotaxis. Furthermore, our work suggests that dCACHE domain proteins can utilise both subdomains for ligand recognition.
format	article
author	Mayra A. Machuca Kevin S. Johnson Yu C. Liu David L. Steer Karen M. Ottemann Anna Roujeinikova
author_facet	Mayra A. Machuca Kevin S. Johnson Yu C. Liu David L. Steer Karen M. Ottemann Anna Roujeinikova
author_sort	Mayra A. Machuca
title	Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate
title_short	Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate
title_full	Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate
title_fullStr	Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate
title_full_unstemmed	Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate
title_sort	helicobacter pylori chemoreceptor tlpc mediates chemotaxis to lactate
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/70d3bd8e624444ddaa9c81528f895161
work_keys_str_mv	AT mayraamachuca helicobacterpylorichemoreceptortlpcmediateschemotaxistolactate AT kevinsjohnson helicobacterpylorichemoreceptortlpcmediateschemotaxistolactate AT yucliu helicobacterpylorichemoreceptortlpcmediateschemotaxistolactate AT davidlsteer helicobacterpylorichemoreceptortlpcmediateschemotaxistolactate AT karenmottemann helicobacterpylorichemoreceptortlpcmediateschemotaxistolactate AT annaroujeinikova helicobacterpylorichemoreceptortlpcmediateschemotaxistolactate
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Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate

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