Amino acid sequence specificities of an adhesive recognition signal
Amino acid sequence specificities of an adhesive recognition signal
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粘附识别信号的氨基酸序列特异性
DOI：
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发表时间：
1985
影响因子：
4
通讯作者：
D. Kennedy
中科院分区：
文献类型：
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作者：
K. Yamada;D. Kennedy
先前已发现源自纤连蛋白的细胞结合结构域的合成肽在体外竞争性且可逆地抑制纤连蛋白介导的粘附，以及在体内抑制细胞迁移事件。已经使用最初鉴定的活性肽序列的变体进一步检查了这种抑制活性所需的氨基酸序列特异性。发现最具活性的小肽是五肽Gly-Arg-Gly-Asp-Ser。虽然发现四肽Arg‐Gly‐Asp‐Ser保留了大量活性，但其活性约为三倍。发现具有以镜像对称序列Ser‐Asp‐Gly‐Arg排列的这四个相同氨基酸的“反向”肽序列几乎与正向序列一样具有活性。然而，同样的反向四肽序列嵌入合成的十肽衍生自一个序列的组织相容性抗原具有最小的活性，表明相邻序列的重要性，在修改这些肽的活性。具有相同电荷的氨基酸的取代或两个带电荷的氨基酸的位置的反转都不保留生物活性。减少带电残基之间的间距也会导致活性损失。我们的研究结果表明，这种粘附识别信号由一个酸性和一个碱性带电基团的特定排列和相邻氨基酸提供的额外信息组成的假设。
Synthetic peptides derived from the cell‐binding domain of fibronectin have previously been found to inhibit fibronectin‐mediated adhesion in vitro competitively and reversibly, as well as inhibiting cell migratory events in vivo. The amino acid sequence specificity required for this inhibitory activity has been examined further using variations of the originally identified active peptide sequences. The most active small peptide was found to be the pentapeptide Gly‐Arg‐Gly‐Asp‐Ser. Although the tetrapeptide Arg‐Gly‐Asp‐Ser was found to retain substantial activity, it was approximately threefold less active. An “inverted” peptide sequence with these same four amino acids arranged in the mirror sym‐metrical sequence Ser‐Asp‐Gly‐Arg was found to be nearly as active as the forward sequence. However, the same inverted tetrapeptide sequence embedded in a synthetic decapeptide derived from a sequence of histocompatibility antigens has minimal activity, suggesting the importance of adjacent sequences in modifying the activity of such peptides. Neither substitution of amino acids of the same charge nor reversal of the positions of the two charged amino acids retains biological activity. Decreasing the spacing between the charged residues also causes a loss of activity. Our results suggest the hypothesis that this adhesive recognition signal consists of a specific arrangement of one acidic and one basic charged group and additional information provided by adjacent amino acids.