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Identification of sites in the cysteine‐rich domain of the class P‐III snake venom metalloproteinases responsible for inhibition of platelet function
Author(s) -
Kamiguti Aura S.,
Gallagher Paul,
Marcinkiewicz Cezary,
Theakston R.David G.,
Zuzel Mirko,
Fox Jay W.
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00799-3
Subject(s) - disintegrin , snake venom , metalloproteinase , venom , cysteine , gpvi , peptide , biochemistry , chemistry , peptide sequence , integrin , platelet , viper venoms , matrix metalloproteinase , biology , microbiology and biotechnology , enzyme , immunology , cell , gene
Atrolysin A and jararhagin are class P‐III snake venom metalloproteinases (SVMPs) with three distinct domains: a metalloproteinase, a disintegrin‐like and a cysteine‐rich. The metalloproteinase and the disintegrin‐like domains of atrolysin A and jararhagin contain peptide sequences that interact with α2β1 integrin and inhibit the platelet responses to collagen. Recently, the recombinant cysteine‐rich domain of atrolysin A was shown to have similar effects, but the sequence(s) responsible for this is unknown. In this report, we demonstrate two complete peptide sequences from the homologous cysteine‐rich domains of atrolysin A and jararhagin that inhibit both platelet aggregation by collagen and adhesion of α2‐expressing K562 cells to this protein. In addition, the peptide effects on platelets do not seem to involve an inhibition of GPVI. These results identify, for the first time, sites in the cysteine‐rich domain of SVMPs that inhibit cell responses to collagen and reveal the complexity of the potential biological effects of these enzymes with multifunctional domains.