title: Crystal structure of Bordetella pertussis BugD solute receptor unveils the basis of ligand binding in a new family of periplasmic binding proteins.
abstract: Periplasmic binding proteins of a new family particularly well represented in Bordetella pertussis have been called Bug receptors. One B.pertussis Bug protein is part of a tripartite tricarboxylate transporter while the functions of the other 77 are unknown. We report the first structure of a Bug receptor, BugD. It adopts the characteristic Venus flytrap motif observed in other periplasmic binding proteins, with two globular domains bisected by a deep cleft. BugD displays a closed conformation resulting from the fortuitous capture of a ligand, identified from the electron density as an aspartate. The structure reveals a distinctive alpha carboxylate-binding motif, involving two water molecules that bridge the carboxylate oxygen atoms to the protein. Both water molecules are hydrogen bonded to a common carbonyl group from Ala14, and each forms a hydrogen bond with one carboxylate oxygen atom of the ligand. Additional hydrogen bonds are found between the ligand alpha carboxylate oxygen atoms and protein backbone amide groups and with a threonine hydroxyl group. This specific ligand-binding motif is highly conserved in Bug proteins, indicating that they may all be receptors of amino acids or other carboxylated solutes, with a similar binding mode. The present structure thus unveils the bases of ligand binding in this large family of periplasmic binding proteins, several hundred members of which have been identified in various bacterial species.
authors.affiliation: CNRS-UMR8117 Institut de Biologie de Lille, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP245 59021 Lille cedex, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Huvent
authors.forename: Hassan
authors.initials: H
authors.lastname: Belrhali
authors.forename: Rudy
authors.initials: R
authors.lastname: Antoine
authors.forename: Coralie
authors.initials: C
authors.lastname: Bompard
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.forename: Françoise
authors.initials: F
authors.lastname: Jacob-Dubuisson
authors.forename: Vincent
authors.initials: V
authors.lastname: Villeret
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001886:Bordetella pertussis / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008024:Ligands; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D026901:Membrane Transport Proteins