title: Ligand specificity determined by differentially arranged common ligand-binding residues in bacterial amino acid chemoreceptors Tsr and Tar.
abstract: Escherichia coli has closely related amino acid chemoreceptors with distinct ligand specificity, Tar for l-aspartate and Tsr for l-serine. Crystallography of the ligand-binding domain of Tar identified the residues interacting with aspartate, most of which are conserved in Tsr. However, swapping of the nonconserved residues between Tsr and Tar did not change ligand specificity. Analyses with chimeric receptors led us to hypothesize that distinct three-dimensional arrangements of the conserved ligand-binding residues are responsible for ligand specificity. To test this hypothesis, the structures of the apo- and serine-binding forms of the ligand-binding domain of Tsr were determined at 1.95 and 2.5 Å resolutions, respectively. Some of the Tsr residues are arranged differently from the corresponding aspartate-binding residues of Tar to form a high affinity serine-binding pocket. The ligand-binding pocket of Tsr was surrounded by negatively charged residues, which presumably exclude negatively charged aspartate molecules. We propose that all these Tsr- and Tar-specific features contribute to specific recognition of serine and aspartate with the arrangement of the side chain of residue 68 (Asn in Tsr and Ser in Tar) being the most critical.
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602; Department of Frontier Bioscience, Hosei University, Koganei 184-8584; Research Center for Micro-Nano Technology, Hosei University, Koganei 184-8584.
authors: Hirotaka
authors: H
authors: Tajima
authors: Graduate School of Frontier Bioscience, Osaka University, Suita 565-0871; Department of Macromolecular Science, Graduate School of Science, Osaka University, Toyonaka 560-0043. Electronic address: kimada@chem.sci.osaka-u.ac.jp.
authors: Katsumi
authors: K
authors: Imada
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602.
authors: Mayuko
authors: M
authors: Sakuma
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602.
authors: Fumiyuki
authors: F
authors: Hattori
authors: College of Pharmaceutical Sciences, Matsuyama University, Matsuyama 790-8578, Japan.
authors: Toshifumi
authors: T
authors: Nara
authors: College of Pharmaceutical Sciences, Matsuyama University, Matsuyama 790-8578, Japan.
authors: Naoki
authors: N
authors: Kamo
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602.
authors: Michio
authors: M
authors: Homma
authors: Department of Frontier Bioscience, Hosei University, Koganei 184-8584; Research Center for Micro-Nano Technology, Hosei University, Koganei 184-8584. Electronic address: ikurok@hosei.ac.jp.
authors: Ikuro
authors: I
authors: Kawagishi
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000378:metabolism; D018360:Crystallography, X-Ray / Q000379:methods; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008024:Ligands; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C057331:Tar protein, E coli; C057635:Tsr protein, Bacteria