Oral Presentation The 43rd Lorne Conference on Protein Structure and Function 2018

Specific and promiscuous ligand recognition by chemotaxis receptors.  (#15)

Anna Roujeinikova 1
  1. Monash University, Clayton, VIC, Australia

Chemotaxis, mediated by membrane-embedded methyl-accepting chemotaxis protein (MCP) receptors,1 plays an important role in bacterial survival and pathogenesis. My lab investigates the structural basis of how the predominant family of bacterial chemoreceptors with an extracytoplasmic double Cache sensing domain (dCache SD) recognize chemical cues, and how they discriminate between attractants and repellents. We have determined the first crystal structures of dCache SDs of MCP receptors from a broad range of bacteria of medical and biotechnological importance, including carcinogenic bacterium Helicobacter pylori and important human and animal pathogen Campylobacter jejuni. Analysis of these structures, in conjunction with mutagenesis, biophysical and molecular simulation studies, provided an insight into diverse mechanisms of ligand recognition by this protein fold. In all previously characterised dCache SDs, direct sensing involved binding of the signal molecule to the membrane-distal, rather than membrane-proximal, subdomain. I will present novel data that reveals the first example of a chemoreceptor that directly recognises its ligand via the membrane-proximal subdomain, helping H. pylori to seek out lactate.2 In addition, I will present the results of our systematic study of the attractant-bound and repellent bound structures and discuss implications for the mechanism of discrimination between atrractants and repellents. I will then describe examples of very specific (Pseudomonas fluorescens CtaB) versus rather promiscuous (P. fluorescens CtaA, C. jejuni Tlp33) chemoreceptors with the same overall fold and discuss the structural basis behind this phenomenon. Finally, I will present an example of a dCache chemoreceptor (C. jejuni Tlp14) that recognises signals indirectly (via periplasmic binding proteins).

  1. 1. Ud-Din, A.I. and Roujeinikova, A. (2017) Methyl-accepting chemotaxis proteins: a core sensing element in prokaryotes and archaea. Cell. Mol. Life Sci. 74, 3293-3303.
  2. 2. Machuca, M.A., Johnson K.S., Liu, Y.C., Steer, D.L., Ottemann K.M. and Roujeinikova, A. (2017) Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate. Sci Reports, 7, 14089.
  3. Liu, Y.C., Machuca, M.A., Beckham, S.A., Gunzburg, M.J. and Roujeinikova, A. (2015) Structural basis for amino-acid recognition and transmembrane signalling by tandem Per-Arnt-Sim (tandem PAS) chemoreceptor sensory domains. Acta Cryst. D71, 2127-2136.
  4. Machuca, M.A., Liu, Y.C., Beckham, S.A., Gunzburg, M.J. and Roujeinikova, A. (2016) The crystal structure of the tandem-PAS sensing domain of Campylobacter jejuni chemoreceptor Tlp1 suggests indirect mechanism of ligand recognition. J. Struct. Biol. 194, 205-213.