Department of Microbiology and Molecular Genetics, Institute for Medical Research IMRIC, Faculty of Medicine, The Hebrew University, POB 12272, Jerusalem 91120, Israel.
Structure. 2010 Feb 10;18(2):188-99. doi: 10.1016/j.str.2009.11.012.
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.
肽-蛋白相互作用非常普遍，介导了信号转导和蛋白运输等关键过程。肽如何克服从无规、灵活的肽转变为刚性、明确的结合结构所涉及的熵成本？基于结构的肽-蛋白相互作用分析表明，大多数肽在结合时不会诱导其伴侣发生构象变化，从而使结合的熵成本最小化。此外，肽显示的界面比蛋白-蛋白界面更好地堆积，并且含有更多的氢键，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，肽倾向于在蛋白表面可用的最大口袋中结合。我们的研究基于 peptiDB，这是一个新的、全面的包含 103 个高分辨率肽-蛋白复合物结构的数据集。除了对肽-蛋白相互作用的理解得到提高外，我们的发现还对这些相互作用的结构建模、设计和操作具有直接影响。
