Lytic activity and structural differences of amphipathic peptides derived from trialysin

Lytic activity and structural differences of amphipathic peptides derived from trialysin

Autor Martins, R. M. Google Scholar
Sforca, M. L. Google Scholar
Amino, R. Google Scholar
Juliano, M. A. Google Scholar
Oyama, S. Google Scholar
Juliano, L. Google Scholar
Pertinhez, T. A. Google Scholar
Spisni, A. Google Scholar
Schenkman, S. Google Scholar
Instituição Lab Nacl Luz Sincrotron
Universidade Federal de São Paulo (UNIFESP)
Univ Parma
Resumo Trialysin is a pore-forming protein found in the saliva of Triatoma infestans (Hemiptera, Reduviidae), the insect vector of Chagas' disease. the protein is active against a broad range of cell types from bacteria to eukaryotic cells. Recognizing that the N-terminus of trialysin harbors the lytic motif [Amino, R., Martins, R. M., Procopio, J., Hirata, I.Y., Juliano, M. A., and Schenkman, S. (2002) J. Biol. Chem. 277, 6207-6213], we designed a set of peptides scanning this region to investigate the structural basis of its biological function. Peptides encompassing residues 1-32 (P6), 1-27 (P7), and 6-32 (P5) efficiently induced lysis of the protozoan parasite Trypanosoma cruzi and Escherichia coli in the 0.4-9.0 mu M range, while much higher concentrations were required to cause hemolysis. Other more internal peptides, including peptide P2 (residues 21-47) and others up to residue 52, were less effective. P6 turned out to be the most active of all. P7 has a significantly higher activity than P5 against E. coli, while P5 has a hemolytic activity comparable to that of P6. CD spectroscopy showed that all tested peptides acquire a comparable helical content in solvent mixtures or in detergent micelles. the solution structure of P2 and P5-P7 was determined in a 30% trifluoroethanol/water mixture by nuclear magnetic resonance. All peptides exhibit a structure characterized by a central helical fold, and except for P2, which does not show a continuous hydrophobic surface, they are amphipathic. the structural models show that P5 and P7 extend their structural similarities with the most active peptide, P6, in either the C-terminus or the N-terminus. Amino acid substitutions in the N-terminus of P6 improved hemolysis but did not change the activity against T cruzi. These results suggest that while amphipathicity is essential for the lytic activity, the selectivity of the active peptides for specific organisms appears to be associated with the structural features of their N- and C-termini.
Idioma Inglês
Data de publicação 2006-02-14
Publicado em Biochemistry. Washington: Amer Chemical Soc, v. 45, n. 6, p. 1765-1774, 2006.
ISSN 0006-2960 (Sherpa/Romeo, fator de impacto)
Publicador Amer Chemical Soc
Extensão 1765-1774
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000235631400024
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