School of Bioscience & Technology, Vellore Institute of Technology, VIT University, Vellore, 632014, India.
National Centre for Biological Sciences, TIFR, UAS-GKVK Campus, Bellary road, Bangalore, 560065, India.
Biol Direct. 2019 Jan 15;14(1):1. doi: 10.1186/s13062-019-0232-2.
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.
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.
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.
This article was reviewed by Arumay Pal and Mallur Madhusudhan.
蛋白质-蛋白质相互作用对于正常的生物过程至关重要，并调节影响基因表达和功能的细胞反应。以前的几项研究强调了蛋白质-蛋白质复合物界面残基在赋予复合物稳定性和特异性方面的作用。蛋白质界面残基以其与相互作用蛋白质的侧链和主链原子的相互作用而闻名。然而，在蛋白质-蛋白质复合物中涉及界面残基的蛋白质内相互作用的程度及其与蛋白质间相互作用的相对贡献尚不清楚。本文使用已知三维结构的蛋白质-蛋白质复合物数据集探讨了这一特征。
我们分析了一组 45 个瞬态蛋白质-蛋白质复合物结构，其中至少有一个相互作用蛋白的已知结构也以未结合形式存在。我们观察到，很大一部分界面残基（2137 个界面残基中有 1608 个，占 75%）同时参与蛋白质内和蛋白质间相互作用。参与分叉相互作用的这种界面残基的氨基酸倾向性被发现与普遍存在于蛋白质-蛋白质界面的倾向性非常相似。最后，我们观察到，大多数（83%）具有分叉相互作用的界面残基的蛋白质内相互作用也存在于未结合的蛋白质形式中。
据我们所知，这是首次表明，除了蛋白质间相互作用外，绝大多数蛋白质-蛋白质界面残基还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来说，在三级结构中，微环境是预先形成的，并在与互补伴侣的瞬态相互作用中保留下来。
这篇文章由 Arumay Pal 和 Mallur Madhusudhan 进行了评审。
