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Journal of Bacteriology, July 2003, p. 4243-4247, Vol. 185, No. 14
0021-9193/03/$08.00+0 DOI: 10.1128/JB.185.14.4243-4247.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Structural Study of Binding of Flagellin by Toll-Like Receptor 5
Saul G. Jacchieri,1* Ricardo Torquato,2 and Ricardo R. Brentani3
Centro de Pesquisas, Fundação Antônio Prudente,1
Sao Paulo Branch, Ludwig Institute for Cancer Research, São Paulo, SP 01509-090,3
Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP 04044-020, Brazil2
Received 24 February 2003/
Accepted 30 April 2003
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
-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
helical.
* Corresponding author. Mailing address: Fundação Antônio Prudente, Centro de Pesquisas, Rua Prof Antonio Prudente 211, São Paulo, SP 01509-090, Brazil. Phone: 55 11 32725000. Fax: 55 11 32725088. E-mail:
sgjacchieri{at}procenio.com.
Journal of Bacteriology, July 2003, p. 4243-4247, Vol. 185, No. 14
0021-9193/03/$08.00+0 DOI: 10.1128/JB.185.14.4243-4247.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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