Protein−Protein Recognition Control by Modulating Electrostatic Interactions

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• 作者：Song Han ; Shijin Yin ; Hong Yi ; Stphanie Mouhat ; Su Qiu ; Zhijian Cao ; Jean-Marc Sabatier ; Yingliang Wu ; Wenxin Li
• 刊名：Journal of Proteome Research
• 出版年：2010
• 出版时间：June 4, 2010
• 年：2010
• 卷：9
• 期：6
• 页码：3118-3125
• 全文大小：403K
• 年卷期：v.9,no.6(June 4, 2010)
• ISSN：1535-3907

文摘

Protein−protein control recognition remains a huge challenge, and its development depends on understanding the chemical and biological mechanisms by which these interactions occur. Here we describe a protein−protein control recognition technique based on the dominant electrostatic interactions occurring between the proteins. We designed a potassium channel inhibitor, BmP05-T, that was 90.32% identical to wild-type BmP05. Negatively charged residues were translocated from the nonbinding interface to the binding interface of BmP05 inhibitor, such that BmP05-T now used BmP05 nonbinding interface as the binding interface. This switch demonstrated that nonbinding interfaces were able to control the orientation of protein binding interfaces in the process of protein−protein recognition. The novel function findings of BmP05-T peptide suggested that the control recognition technique described here had the potential for use in designing and utilizing functional proteins in many biological scenarios.