Identification of sites in the cysteine-rich domain of the class P-III snake venom metalloproteinases responsible for inhibition of platelet function

Kamiguti, Aura S., Gallagher, Paul, Marcinkiewicz, Cezary, Theakston, R.David G., Zuzel, Mirko and Fox, Jay W. (2003) 'Identification of sites in the cysteine-rich domain of the class P-III snake venom metalloproteinases responsible for inhibition of platelet function'. Febs Letters, Vol 549, Issue 1-3, pp. 129-134.

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Abstract

Atrolysin A and jararhagin are class P-III snake venom metalloproteinases (SVMPs) with three distinct domains: a metalloproteinase, a disintegrin-like and a cysteinerich. The metalloproteinase and the disintegrin-like domains of atrolysin A and jararhagin contain peptide sequences that interact with alpha2beta1 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 alpha2-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. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

Item Type:	Article
Uncontrolled Keywords:	Snake venom metalloproteinase; Cysteine-rich domain; Platelet aggregation; Protein tyrosine phophorylation; α2β1 integrin
Subjects:	QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles
Faculty: Department:	Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI):	https://doi.org/10.1016/s0014-5793(03)00799-3
Depositing User:	Ms Julia Martin
Date Deposited:	19 Nov 2012 10:44
Last Modified:	06 Feb 2018 13:04
URI:	https://archive.lstmed.ac.uk/id/eprint/2578

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