The alpha 2 beta 1 integrin cell surface collagen receptor binds to the alpha 1 (I)-CB3 peptide of collagen.
The alpha 2 beta 1 integrin cell surface collagen receptor binds to the alpha 1 (I)-CB3 peptide of collagen.
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DOI：
10.1016/s0021-9258(19)34038-4
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发表时间：
1990-03
期刊：
影响因子：
--
通讯作者：
W. Staatz;J. Walsh;T. Pexton;S. Santoro
中科院分区：
文献类型：
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作者：
W. Staatz;J. Walsh;T. Pexton;S. Santoro
我们之前已经表明，血小板通过表面糖蛋白Ia-IIa（人白细胞极晚期激活蛋白2，α2β1整合素）复合物介导的Mg2+依赖性机制粘附到胶原基质上。这种粘附是胶原蛋白特异的，并由 I、II、III、IV 和 VI 型胶原蛋白支持。粘附蛋白受体整联蛋白家族的其他几个成员识别其粘附糖蛋白配体内离散的线性氨基酸序列。使用完整血小板和含有纯化受体复合物的脂质体进行的实验表明，α2β1受体以Mg2(+)依赖性方式识别变性的I型胶原。为了进一步定位结合位点，通过凝胶过滤和离子交换层析纯化 I 型胶原的 α1 和 α2 链，并作为粘合基质进行测试。 α1(I)和α2(I)链均有效支持Mg2(+)依赖性血小板粘附。然后用溴化氰裂解纯化的α1(I)胶原链，并通过羧甲基纤维素色谱法分离所得肽。只有α1(I)-CB3片段支持Mg2(+)依赖性血小板粘附。单克隆抗体P1H5识别整联蛋白受体的α2亚基上的表位，并且抑制完整血小板和带有纯化受体的脂质体对胶原的粘附，也抑制血小板对α1(I)-CB3片段的粘附。这些结果表明α2β1受体识别I型胶原的α1(I)-CB3片段中存在的氨基酸序列。相同或相似的序列可能介导受体与其他胶原多肽的结合。
We have previously shown that platelets adhere to collagen substrates via a Mg2(+)-dependent mechanism mediated by the surface glycoprotein Ia-IIa (human leukocyte very late activation protein 2, alpha 2 beta 1 integrin) complex. The adhesion is specific for collagen and is supported by collagen types I, II, III, IV, and VI. Several other members of the integrin family of adhesive protein receptors recognize discrete linear amino acid sequences within their adhesive glycoprotein ligands. Experiments with both intact platelets and with liposomes containing the purified receptor complex indicated that the alpha 2 beta 1 receptor recognized denatured type I collagen in a Mg2(+)-dependent manner. To further localize the binding site, the alpha 1 and alpha 2 chains of type I collagen were purified by gel filtration and ion exchange chromatography and tested as adhesive substrates. Both the alpha 1(I) and alpha 2(I) chains effectively supported Mg2(+)-dependent platelet adhesion. The purified alpha 1(I) collagen chain was then subjected to cleavage with cyanogen bromide, and the resultant peptides were separated by chromatography on carboxymethylcellulose. Only the alpha 1(I)-CB3 fragment supported Mg2(+)-dependent platelet adhesion. The monoclonal antibody P1H5 which recognizes an epitope on the alpha 2 subunit of the integrin receptor and which inhibits the adhesion of both intact platelets and liposomes bearing the purified receptor to collagen also inhibited platelet adhesion to the alpha 1(I)-CB3 fragment. These results indicate that the alpha 2 beta 1 receptor recognizes a sequence of amino acids present in the alpha 1(I)-CB3 fragment of type I collagen. An identical or similar sequence likely mediates binding of the receptor to other collagen polypeptides.