A short proregion of trialysin, a pore-forming protein of Triatoma infestans salivary glands, controls activity by folding the N-terminal lytic motif.
Triatoma infestans (Hemiptera: Reduviidae) is a hematophagous insect that transmits the protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas' disease. Its saliva contains trialysin, a protein that forms pores in membranes. Peptides based on the N-terminus of trialysin lyse cells and fold into alpha-helical amphipathic segments resembling antimicrobial peptides. Using a specific antiserum against trialysin, we show here that trialysin is synthesized as a precursor that is less active than the protein released after saliva secretion. A synthetic peptide flanked by a fluorophore and a quencher including the acidic proregion and the lytic N-terminus of the protein is also less active against cells and liposomes, increasing activity upon proteolysis. Activation changes the peptide conformation as observed by fluorescence increase and CD spectroscopy. This mechanism of activation could provide a way to impair the toxic effects of trialysin inside the salivary glands, thus restricting damaging lytic activity to the bite site.
Martins
Rafael M
RM
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, Brazil.
Amino
Rogerio
R
Daghastanli
Katia R
KR
Cuccovia
Iolanda M
IM
Juliano
Maria A
MA
Schenkman
Sergio
S
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007303:Insect Vectors / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D052899:Pore Forming Cytotoxic Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D011817:Rabbits; D012469:Salivary Glands / Q000737:chemistry / Q000378:metabolism; D012471:Salivary Proteins and Peptides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D014224:Triatoma / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000187:drug effects
D010455:Peptides; D052899:Pore Forming Cytotoxic Proteins; D012471:Salivary Proteins and Peptides; C509988:trialysin protein, Triatoma infestans