Solution structures and integrin binding activities of an RGD peptide with two isomers
Solution structures and integrin binding activities of an RGD peptide with two isomers
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DOI：
10.1021/bi002101f
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发表时间：
2001-02-27
期刊：
影响因子：
2.9
通讯作者：
Ruoslahti, E
中科院分区：
文献类型：
--
作者：
Assa-Munt, N;Jia, X;Ruoslahti, E
Arg-Gly-Asp (RGD) 序列作为细胞外基质蛋白中的主要整合素识别位点，含有该序列的肽可以模拟基质蛋白的活性。根据 RGD 序列的背景，含有 RGD 的肽可以结合所有 RGD 定向整联蛋白、少数或仅结合单个整联蛋白。我们之前从噬菌体展示的肽库中分离出一种环肽，它与 α (v)beta (3) 和 alpha (v)beta (5) 整合素紧密结合，但不与其他密切相关的整合素结合。这种肽 ACDCRGDCFCG 根据内部二硫键以两种天然构型存在。具有 1-4: 2-3 二硫键排列的肽负责大部分 α (v) 整联蛋白结合活性，而 1-3; 2-3 二硫键排列的肽负责大部分 α (v) 整联蛋白结合活性。 2-3肽的效力大约低10倍。通过核磁共振进行的溶液结构分析揭示了 RGD-4C 的两种异构体中 RGD 基序的完全不同的表现形式。这些结果为整合素的配体识别特异性提供了新的见解。
The Arg-Gly-Asp (RGD) sequence serves as the primary integrin recognition site in extracellular matrix proteins, and peptides containing this sequence can mimic the activities of the matrix proteins. Depending on the context of the RGD sequence, an RGD-containing peptide may bind to all of the RGD-directed integrins, to a few, or to only a single one. We have previously isolated from a phage-displayed peptide library a cyclic peptide that binds avidly to the alpha (v)beta (3) and alpha (v)beta (5) integrins but does not bind to other closely related integrins. This peptide, ACDCRGDCFCG, exists in two natural configurations depending on internal disulfide bonding. The peptide with the 1-4: 2-3 disulfide bond arrangement accounts for most of the alpha (v) integrin binding activity, whereas the 1-3; 2-3 peptide is about 10-fold less potent. Solution structure analysis by nuclear magnetic resonance reveals an entirely different presentation of the RGD motif in the two isomers of RGD-4C. These results provide new insight into the ligand recognition specificity of integrins.