The Structural Basis of Peptide-Protein Binding Strategies
The Structural Basis of Peptide-Protein Binding Strategies
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DOI：
10.1016/j.str.2009.11.012
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发表时间：
2010-02-10
期刊：
影响因子：
5.7
通讯作者：
Schueler-Furman, Ora
中科院分区：
文献类型：
--
作者：
London, Nir;Movshovitz-Attias, Dana;Schueler-Furman, Ora
肽-蛋白质相互作用非常普遍，介导信号转导和蛋白质运输等关键过程。肽如何克服从非结构化、柔性肽转变为刚性、明确结合结构所涉及的熵成本？肽-蛋白质相互作用的基于结构的分析揭示了大多数肽在结合时不会诱导其伴侣的构象变化，从而使结合的熵成本最小化。此外，肽显示比蛋白质-蛋白质界面更好地包装的界面，并且包含显著更多的氢键，主要是涉及肽骨架的氢键。此外，“热点”残基贡献了大部分结合能。最后，肽倾向于结合在蛋白质表面上可用的最大口袋中。我们的研究是基于peptiDB，一个新的和全面的数据集103高分辨率的肽-蛋白质复合物结构。除了提高对肽-蛋白质相互作用的理解，我们的研究结果对这些相互作用的结构建模，设计和操纵有直接的影响。
Peptide-protein interactions are very prevalent, mediating key processes such as signal transduction and protein trafficking. How can peptides overcome the entropic cost involved in switching from an unstructured, flexible peptide to a rigid, well-defined bound structure? A structure-based analysis of peptide-protein interactions unravels that most peptides do not induce conformational changes on their partner upon binding, thus minimizing the entropic cost of binding. Furthermore, peptides display interfaces that are better packed than protein-protein interfaces and contain significantly more hydrogen bonds, mainly those involving the peptide backbone. Additionally, "hot spot" residues contribute most of the binding energy. Finally, peptides tend to bind in the largest pockets available on the protein surface. Our study is based on peptiDB, a new and comprehensive data set of 103 high-resolution peptide-protein complex structures. In addition to improved understanding of peptide-protein interactions, our findings have direct implications for the structural modeling, design, and manipulation of these interactions.