title: Structural study of binding of flagellin by Toll-like receptor 5.
abstract: In order to predict the binding regions within the complex formed by Toll-like receptor 5 (TLR-5) and flagellin, a complementary hydropathy between the two proteins was sought. A region common to the flagellins of Salmonella enterica serovar Typhimurium, Pseudomonas aeruginosa, and Listeria monocytogenes was shown to be hydropathically complementary to the 552-to-561 fragment of TLR-5, whose sequence is EILDISRNQL. The hydrophobicity profile of this region is shared with flagellins of 377 bacterial species out of a total of 723 publicly available sequences. A conformational analysis of the predicted binding site of TLR-5, whose structure is still unknown, was carried out with a methodology already applied to similar problems. To sample the conformations available to the peptide chain, a plot of the number of conformations per unit energy interval (density of states) versus energy was built. Following a theoretical argument, conformations belonging to maxima in this plot were selected. The most stable structure obtained in this search, an alpha-helical conformation, was shown to form the electrostatic interactions Glu552-Gln89, Asp555-Arg92, and Arg558-Glu93 with the predicted binding site of the flagellin of S. enterica serovar Typhimurium, formed by the 88-to-97 chain fragment (LQRVRELAVQ), which is likewise alpha helical.
authors.affiliation: Centro de Pesquisas, Fundação Antônio Prudente. Sao Paulo Branch, Ludwig Institute for Cancer Research, São Paulo, SP 01509-090, Brazil. sgjacchieri@procenio.com
authors.forename: Saul G
authors.initials: SG
authors.lastname: Jacchieri
authors.forename: Ricardo
authors.initials: R
authors.lastname: Torquato
authors.forename: Ricardo R
authors.initials: RR
authors.lastname: Brentani
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D005408:Flagellin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008089:Listeria monocytogenes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012984:Software; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors
chemical_list: D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D005408:Flagellin