Common molecular scaffold for two unrelated RGD molecules.
Common molecular scaffold for two unrelated RGD molecules.
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两个不相关的 RGD 分子的共同分子支架。
DOI：
10.1093/protein/8.8.823
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Kodandapani,R
中科院分区：
文献类型：
--
作者：
Ely,KR;Kunicki,TJ;Kodandapani,R
精氨酸-甘氨酸-天冬氨酸（RGD）序列对于细胞表面受体（整联蛋白）识别细胞粘附蛋白是重要的。该三肽序列存在于许多蛋白质中，包括纤连蛋白、玻连蛋白、血管性血友病因子和纤维蛋白原。不同受体对RGD序列的特异性和选择性结合表明，三肽的构象取向对立体化学识别至关重要。测定了含有RGD信号的两种蛋白质的晶体结构：（i）纤连蛋白的细胞结合III型模块（FNm，0）和（ii）抗受体抗体片段（OPG 2），其是在可变（VH）结构域中具有赖德识别位点的功能性RGD配体模拟物。这两个模块都折叠成具有两层反对位β-片层的β-桶，所述反对位β-片层包围疏水核心。由于这些分子均含有RGD（赖德）序列，因此有独特的机会进行直接结构比较。通过比较，在这两种不相关的分子中确定了一种共同的分子支架。在该框架内，RGD（赖德）位点位于两个模块中结构相关的环中，即在连接pVsheet之一中的最后两条链的长环中的支架的一端。这种共享的支架用于受体识别的RGD位点的立体化学呈现。
The sequence arginine-glycine-aspartic acid (RGD) is important for recognition of cell adhesion proteins by cell surface receptors (integrins). This tripeptide sequence is present in a number of proteins including fibronectin, vitronectin, von Willebrand factor and fibrinogen. Specific and selective binding of the RGD sequence by different receptors suggests that the conformational orientation of the tripeptide is critical for stereochemical recognition. The crystal structures of two proteins that contain the RGD signal were determined: (i) the cell-binding type III module of fibronectin (FNm,0) and (ii) an anti-receptor antibody fragment (OPG2) that is a functional RGD ligand mimic with an RYD recognition site in the variable (VH) domain. Both of these modules are folded into β-barrels with two layers of antiparaJlel β-sheets enclosing a hydrophobiccore. Since these molecules each contain the RGD (RYD) sequence, there is a unique opportunity for direct structural comparison. The comparison has defined a common molecular scaffold in these two unrelated molecules. Within this framework, the RGD (RYD) sites are located in structurally related loops in the two modules, i.e. at one end of the scaffold in a long loop connecting the last two strands in one of the pVsheets. This shared scaffold is used for the stereochemical presentation of the RGD site for receptor recognition.