Structural study of binding of flagellin by Toll-like receptor 5

• Autor(a) principal: Jacchieri, Saul G.
• Data de Publicação: 2003
• Outros Autores: Torquato, Ricardo [UNIFESP], Brentani, Ricardo R.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1128/JB.185.14.4243-4247.2003; http://repositorio.unifesp.br/handle/11600/27299

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 bacteria] 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-Gin89, 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.