Ankyrin repeat: A unique motif mediating protein-protein interactions
Ankyrin repeat: A unique motif mediating protein-protein interactions
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DOI：
10.1021/bi062188q
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发表时间：
2006-12-26
期刊：
影响因子：
2.9
通讯作者：
Tsai, Ming-Daw
中科院分区：
文献类型：
--
作者：
Li, Junan;Mahajan, Anjali;Tsai, Ming-Daw
锚蛋白重复序列（Ankyrin repeat）是自然界中存在最广泛的蛋白质基序之一，由30-34个氨基酸残基组成，专门介导蛋白质-蛋白质相互作用，其中一些直接参与人类癌症和其他疾病的发展。每个锚蛋白重复序列都呈现螺旋-转角-螺旋构象，并且这种串联重复序列的串以接近线性的阵列包装以形成具有相对柔性环的螺旋-转角-螺旋束。锚蛋白重复序列蛋白的整体结构主要通过重复序列内和重复序列间的疏水和氢键相互作用来稳定。锚蛋白重复序列蛋白的重复和延长性质提供了锚蛋白重复序列蛋白在蛋白质稳定性、折叠和解折叠以及结合特异性方面的独特特征的分子基础。最近的研究表明，锚蛋白重复蛋白不识别特定的序列，相互作用的残基不连续地分散在整个分子的锚蛋白重复蛋白和它的伴侣。此外，数以千计的锚蛋白重复序列的可用性使得使用合理的设计来修饰生理上重要的锚蛋白重复蛋白的特异性和稳定性，甚至通过组合化学方法产生具有新功能的锚蛋白重复蛋白成为可能。
Ankyrin repeat, one of the most widely existing protein motifs in nature, consists of 30-34 amino acid residues and exclusively functions to mediate protein-protein interactions, some of which are directly involved in the development of human cancer and other diseases. Each ankyrin repeat exhibits a helix-turn-helix conformation, and strings of such tandem repeats are packed in a nearly linear array to form helix-turn-helix bundles with relatively flexible loops. The global structure of an ankyrin repeat protein is mainly stabilized by intra- and inter-repeat hydrophobic and hydrogen bonding interactions. The repetitive and elongated nature of ankyrin repeat proteins provides the molecular bases of the unique characteristics of ankyrin repeat proteins in protein stability, folding and unfolding, and binding specificity. Recent studies have demonstrated that ankyrin repeat proteins do not recognize specific sequences, and interacting residues are discontinuously dispersed into the whole molecules of both the ankyrin repeat protein and its partner. In addition, the availability of thousands of ankyrin repeat sequences has made it feasible to use rational design to modify the specificity and stability of physiologically important ankyrin repeat proteins and even to generate ankyrin repeat proteins with novel functions through combinatorial chemistry approaches.