Structure and proposed mechanism for the pH-sensing Helicobacter pylori chemoreceptor TlpB.
pH sensing is crucial for survival of most organisms, yet the molecular basis of such sensing is poorly understood. Here, we present an atomic resolution structure of the periplasmic portion of the acid-sensing chemoreceptor, TlpB, from the gastric pathogen Helicobacter pylori. The structure reveals a universal signaling fold, a PAS domain, with a molecule of urea bound with high affinity. Through biophysical, biochemical, and in vivo mutagenesis studies, we show that urea and the urea-binding site residues play critical roles in the ability of H. pylori to sense acid. Our signaling model predicts that protonation events at Asp114, affected by changes in pH, dictate the stability of TlpB through urea binding.
Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA.
Emily
E
Goers Sweeney
J Nathan
JN
Henderson
John
J
Goers
Christopher
C
Wreden
Kevin G
KG
Hicks
Jeneva K
JK
Foster
Raghuveer
R
Parthasarathy
S James
SJ
Remington
Karen
K
Guillemin
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D004926:Escherichia coli; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D011485:Protein Binding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D014508:Urea / Q000737:chemistry* / Q000378:metabolism
D001426:Bacterial Proteins; D011522:Protons; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014508:Urea