Kamiguti Aura S, Gallagher Paul, Marcinkiewicz Cezary, Theakston R David G, Zuzel Mirko, Fox Jay W
Department of Haematology, University of Liverpool, Daulby Street, Liverpool L69 3GA, UK.
FEBS Lett. 2003 Aug 14;549(1-3):129-34. doi: 10.1016/s0014-5793(03)00799-3.
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 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.
阿特罗溶素A和矛头蝮蛇毒金属蛋白酶是P-III类蛇毒金属蛋白酶（SVMPs），具有三个不同的结构域：一个金属蛋白酶结构域、一个解整合素样结构域和一个富含半胱氨酸的结构域。阿特罗溶素A和矛头蝮蛇毒金属蛋白酶的金属蛋白酶结构域和解整合素样结构域含有与α2β1整合素相互作用并抑制血小板对胶原蛋白反应的肽序列。最近，阿特罗溶素A的重组富含半胱氨酸结构域显示出类似的作用，但其负责此作用的序列尚不清楚。在本报告中，我们展示了来自阿特罗溶素A和矛头蝮蛇毒金属蛋白酶同源富含半胱氨酸结构域的两个完整肽序列，它们既能抑制胶原蛋白诱导的血小板聚集，又能抑制表达α2的K562细胞与该蛋白的黏附。此外，这些肽对血小板的作用似乎不涉及对糖蛋白VI（GPVI）的抑制。这些结果首次确定了SVMPs富含半胱氨酸结构域中抑制细胞对胶原蛋白反应的位点，并揭示了这些具有多功能结构域的酶潜在生物学效应的复杂性。
