Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate

Mayra A. Machuca, Kevin S. Johnson, Yu C. Liu, David L. Steer, Karen M. Ottemann, Anna Roujeinikova

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number14089
Number of pages15
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • bacteria
  • x-ray crystallography

Cite this

Machuca, M. A., Johnson, K. S., Liu, Y. C., Steer, D. L., Ottemann, K. M., & Roujeinikova, A. (2017). Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate. Scientific Reports, 7(1), [14089]. https://doi.org/10.1038/s41598-017-14372-2
Machuca, Mayra A. ; Johnson, Kevin S. ; Liu, Yu C. ; Steer, David L. ; Ottemann, Karen M. ; Roujeinikova, Anna. / Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
@article{6c44c2bf1ff84490b6d78966ce7d9474,
title = "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 recognition. Here, we report the 2.2 {\AA} 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.",
keywords = "bacteria, x-ray crystallography",
author = "Machuca, {Mayra A.} and Johnson, {Kevin S.} and Liu, {Yu C.} and Steer, {David L.} and Ottemann, {Karen M.} and Anna Roujeinikova",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-14372-2",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate. / Machuca, Mayra A.; Johnson, Kevin S.; Liu, Yu C.; Steer, David L.; Ottemann, Karen M.; Roujeinikova, Anna.

In: Scientific Reports, Vol. 7, No. 1, 14089, 01.12.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate

AU - Machuca, Mayra A.

AU - Johnson, Kevin S.

AU - Liu, Yu C.

AU - Steer, David L.

AU - Ottemann, Karen M.

AU - Roujeinikova, Anna

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

KW - bacteria

KW - x-ray crystallography

UR - http://www.scopus.com/inward/record.url?scp=85032482599&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-14372-2

DO - 10.1038/s41598-017-14372-2

M3 - Article

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 14089

ER -