Periplasmic binding protein
Bordetella pertussis Tohama I (bacteria)
Periplasmic cleft is the interdomain between outer membrane and inner membrane of the gram negative bacteria. High concentration solutes such as sugars, amino acids, and ions exist there. These solutes are vital for bacteria, and are uptaken via diverse membrane transporters. The activity of the transporters is regulated by periplasmic binding proteins which bind to the transporters after recognizing the specific solutes in the periplasm. Bug (Bordetella uptake gene) gene products are considered to be periplasmic binding proteins. In Bordetella pertussis, 78 putative Bug gene products exist, however, almost all of them are "orphans" (i.e. without identified membrane partners) thus the function of them are not well-known.
Huvent et al. reported the crystal structure of BugD, an orphan Bug of Bordetella pertussis. The result indicated that the structure of BugD shares three major common structural features of periplasmic binding proteins characterized so far that are receptors of carbohydrates, amino acids, ions or oligopeptides. Firstly, BugD consists of two globular domains separated by deep groove. The periplasmic binding protein structures solved so far have been divided between two groups, depending on how the polypeptide chain is apportioned between the two domains and, as a consequence, on the pattern of inter-domain connectivity. BugD belongs to the periplasmic binding proteins of group2, with two cross-overs between the domains achieved by forming domain1 from two segments from the amino and carboxy-terminal ends of the protein and domain2 from the remaining middle segment. Secondly, the ligand is bound within the cleft and engulfed by both domains. The ligand interacted with F13, A14, G17, T19, and D20 in the domain1 and A138, S139, T162, A163, D179 and Q180 in the domain2 via hydrogen bonds, and the electron density map suggest that the ligand is aspartate. Finally, the structure of the ligand binding site changes depending on whether the ligand is bound or not. The two domains of unliganded protein are further apart, rendering the binding-site cleft between the domains open and accessible to the ligand, while bending of a hinge between the two domains after the ligand binding result in a closed conformation. Furthermore, the sequence analysis of Bug genes of Bordetella pertussis reveals that among 78 genes, 35 Bugs present a strict conservation of typical amino acids (G17, G161, and T19). G17 and G161 are important residues which accommodate two water molecules in the ligand binding site. The waters bridge a carbonyl oxygen atom of A14 and two carboxyl oxygen atoms of ligand aspartate. This indicates that the Bug gene products which conserve the typical marker residues found in the BugD belong to alpha-carboxylate receptors. Therefore, BugD will serve as a structural prototype of a new, very large family of periplasmic receptors.
Protein Data Bank (PDB)
Huvent, I. Belrhali, H. Antoine, R. Bompard, C. Locht, C. Jacob-Dubuisson, F. Villeret, V.; "Crystal Structure of Bordetella pertussis BugD Solute Receptor Unveils the Basis of Ligand Binding in a New Family of Periplasmic Binding Proteins"; J.Mol.Biol.; (2006) 356:1014-1026 PubMed:16403514.
author: Daisuke Ino