Systematic analysis of tropomodulin/tropomyosin interactions uncovers fine-tuned binding specificity of intrinsically disordered proteins.
Systematic analysis of tropomodulin/tropomyosin interactions uncovers fine-tuned binding specificity of intrinsically disordered proteins.
复制标题
原调节蛋白/原肌球蛋白相互作用的系统分析揭示了本质上无序蛋白质的微调结合特异性。
DOI：
10.1002/jmr.1093
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Kostyukova,AllaS
中科院分区：
文献类型：
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作者：
Uversky,VladimirN;Shah,SamarP;Gritsyna,Yulia;Hitchcock-DeGregori,SarahE;Kostyukova,AllaS
一个有趣的调节机制是一些蛋白质以同种型特异性方式识别其结合伴侣的能力。在这项研究中，我们对原调节蛋白（Tmod）与原肌球蛋白（TM）相互作用的特异性进行了系统分析，以表明不同Tmod亚型与TM的亲和力是亚型依赖性的。利用内在无序预测、序列比对和圆二色性来建立这些亚型特异性相互作用的结构基础。分析源自不同TM同种型的N末端的模型肽对对应于不同Tmod同种型的两个TM结合位点的蛋白质片段的亲和力。确定几个残基是亲和力中亚型依赖性差异的原因。我们建议，改变一组残基，而不是一个单一的残基是需要改变一个异构体的结合亲和力，以模仿另一个异构体的亲和力。一般的内在紊乱预测因子PONDR® VLXT被证明是一种有用的工具，可用于分析亚型特异性结合所涉及的区域，并预测对结合中亚型差异重要的残基。了解负责同种型特异性亲和力的残基创建了一种适合于研究Tmod/TM相互作用对肌细胞中肌节组装或非肌细胞中肌动蛋白动力学的影响的工具。版权所有© 2011约翰威利父子有限公司.
An intriguing regulatory mechanism is the ability of some proteins to recognize their binding partners in an isoform‐specific manner. In this study we undertook a systematic analysis of the specificity of the tropomodulin (Tmod) interaction with tropomyosin (TM) to show that affinities of different Tmod isoforms to TM are isoform‐dependent. Intrinsic disorder predictions, alignment of sequences, and circular dichroism were utilized to establish a structural basis for these isoform‐specific interactions. The affinity of model peptides derived from the N‐terminus of different TM isoforms to protein fragments that correspond to the two TM‐binding sites of different Tmod isoforms were analyzed. Several residues were determined to be responsible for the isoform‐dependent differences in affinity. We suggest that changing a set of residues rather than a single residue is needed to alter the binding affinity of one isoform to mimic the affinity of another isoform. The general intrinsic disorder predictor, PONDR® VLXT, was shown to be a useful tool for analyzing regions involved in isoform‐specific binding and for predicting the residues important for isoform differences in binding. Knowing the residues responsible for isoform‐specific affinity creates a tool suitable for studying the influence of Tmod/TM interactions on sarcomere assembly in muscle cells or actin dynamics in non‐muscle cells. Copyright © 2011 John Wiley & Sons, Ltd.