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

FEBS Letters

Kamiguti, Aura S.³  Zuzel, Mirko³  Marcinkiewicz, Cezary²  Gallagher, Paul⁴  Theakston, R.David G.¹  Fox, Jay W.⁴ 

[1] Liverpool School of Tropical Medicine, Liverpool, UK;Temple University, College of Science and Technology, Department of Biology, Philadelphia, PA, USA;Department of Haematology, University of Liverpool, Daulby Street, Liverpool L69 3GA, UK;Department of Microbiology, University of Virginia, Charlottesville, VA, USA

关键词: Snake venom metalloproteinase;    Cysteine-rich domain;    Platelet aggregation;    Protein tyrosine phophorylation;    α2β1 integrin;    SVMP;    snake venom metalloproteinase;    GPVI;    glycoprotein VI;    CMFDA;    5-chloromethyl fluorescein diacetate;    HBSS;    Hank's balanced salt solution;    PRP;    platelet-rich plasma;    PGE1;    prostaglandin E1;    RIPA;    radioimmunoprecipitation assay;   

DOI  :  10.1016/S0014-5793(03)00799-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown