Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Machuca, Mayra; Johnson, Kevin; Liu, Yu; Steer, David; Ottemann, Karen; Roujeinikova, Anna
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 15
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-14372-2
• Languages: English
• ISSNs: 2045-2322

Abstract

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 theHelicobacter 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 anH .pylori chemoattractant that is sensed via TlpC with aK D = 155 µM. Lactate is utilised byH .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.