6W3T

Crystal structure of ligand-binding domain of Campylobacter jejuni chemoreceptor Tlp3 in complex with L-norvaline

Summary for 6W3T

• Entry DOI: 10.2210/pdb6w3t/pdb
• Descriptor: Methyl-accepting chemotaxis protein, NORVALINE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: bacterial chemotaxis, chemoreceptor, double cache, ligand binding domain, signaling protein
• Biological source: Campylobacter jejuni
• Total number of polymer chains: 2
• Total formula weight: 58011.60

Authors

Khan, M.F.,Machuca, M.A.,Rahman, M.M.,Roujeinikova, A. (deposition date: 2020-03-09, release date: 2020-05-20, Last modification date: 2024-10-09)

Primary citation

Khan, M.F.,Machuca, M.A.,Rahman, M.M.,Koc, C.,Norton, R.S.,Smith, B.J.,Roujeinikova, A.
Structure-Activity Relationship Study Reveals the Molecular Basis for Specific Sensing of Hydrophobic Amino Acids by theCampylobacter jejuniChemoreceptor Tlp3.
Biomolecules, 10:-, 2020

PubMed Abstract: Chemotaxis is an important virulence factor of the foodborne pathogen . Inactivation of chemoreceptor Tlp3 reduces the ability of to invade human and chicken cells and to colonise the jejunal mucosa of mice. Knowledge of the structure of the ligand-binding domain (LBD) of Tlp3 in complex with its ligands is essential for a full understanding of the molecular recognition underpinning chemotaxis. To date, the only structure in complex with a signal molecule is Tlp3 LBD bound to isoleucine. Here, we used in vitro and in silico screening to identify eight additional small molecules that signal through Tlp3 as attractants by directly binding to its LBD, and determined the crystal structures of their complexes. All new ligands (leucine, valine, α-amino-N-valeric acid, 4-methylisoleucine, β-methylnorleucine, 3-methylisoleucine, alanine, and phenylalanine) are nonpolar amino acids chemically and structurally similar to isoleucine. X-ray crystallographic analysis revealed the hydrophobic side-chain binding pocket and conserved protein residues that interact with the ammonium and carboxylate groups of the ligands determine the specificity of this chemoreceptor. The uptake of hydrophobic amino acids plays an important role in intestinal colonisation by , and our study suggests that seeks out hydrophobic amino acids using chemotaxis.

PubMed: 32403336
DOI: 10.3390/biom10050744

Experimental method

X-RAY DIFFRACTION (2.1 Å)