BACKGROUND Protein-protein interactions are crucial for normal biological processes and to regulate cellular reactions that affect gene expression and function. Several previous studies have emphasized the roles of residues at the interface of protein-protein complexes in conferring stability and specificity to the complex. Interface residues in a protein are well known for their interactions with sidechain and main chain atoms with the interacting protein. However, the extent of intra-protein interactions involving interface residues in a protein-protein complex and their relative contribution in comparison to inter-protein interactions are not clearly understood. This paper probes this feature using a dataset of protein-protein complexes of known 3-D structure. RESULTS We have analysed a dataset of 45 transient protein-protein complex structures with at least one of the interacting proteins with a known structure available also in the unbound form. We observe that a large proportion of interface residues (1608 out of 2137 interface residues, 75%) are involved in intra and inter-protein interactions simultaneously. The amino acid propensities of such interfacial residues involved in bifurcated interactions are found to be highly similar to the general propensities to occur at protein-protein interfaces. Finally, we observe that a majority (83%) of intra-protein interactions of interface residues with bifurcated interactions, are also observed in the protein uncomplexed form. CONCLUSIONS We have shown, to the best of our knowledge for the first time, that a vast majority of the protein-protein interface residues are involved in extensive intra-protein interactions apart from inter-protein interactions. For a majority of such interface residues the microenvironment in the tertiary structure is pre-formed and retained upon complex formation with its cognate partner during transient interactions. REVIEWERS This article was reviewed by Arumay Pal and Mallur Madhusudhan.

中文翻译：

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瞬时蛋白质-蛋白质复合物的界面残基除了蛋白质间的相互作用外，还具有广泛的蛋白质内相互作用。

背景技术蛋白质-蛋白质相互作用对于正常的生物学过程和调节影响基因表达和功能的细胞反应至关重要。先前的一些研究强调了蛋白质-蛋白质复合物界面上的残基在赋予复合物稳定性和特异性方面的作用。蛋白质中的界面残基因其与侧链和主链原子与相互作用的蛋白质的相互作用而众所周知。但是，尚不清楚蛋白质间相互作用中涉及界面残基的蛋白质间相互作用的程度及其相对于蛋白质间相互作用的相对贡献。本文使用已知的3-D结构的蛋白质-蛋白质复合物数据集探讨了此功能。结果我们分析了45种瞬时蛋白质-蛋白质复合物结构的数据集，其中至少有一种相互作用的蛋白质具有已知结构，也可以非结合形式存在。我们观察到，大部分界面残基（2137个界面残基中的1608个残基，占75％）同时参与了蛋白质内部和蛋白质间的相互作用。发现这种涉及分叉相互作用的界面残基的氨基酸倾向与发生在蛋白质-蛋白质界面的一般倾向高度相似。最后，我们观察到也以非复合形式观察到界面残基的大部分蛋白内相互作用（分叉相互作用）（83％）。结论我们已尽我们所知首次展示了 除了蛋白质间相互作用外，绝大多数蛋白质-蛋白质界面残基都参与广泛的蛋白质内相互作用。对于大多数这样的界面残基，在瞬态相互作用期间，三级结构中的微环境是预先形成的，并在与其同源伴侣形成复合物后保留。审阅者本文由Arumay Pal和Mallur Madhusudhan审阅。