Oligomeric protein structure networks: insights into protein-protein interactions.
Oligomeric protein structure networks: insights into protein-protein interactions.
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DOI：
10.1186/1471-2105-6-296
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发表时间：
2005-12-10
影响因子：
3
通讯作者：
Vishveshwara S
中科院分区：
文献类型：
--
作者：
Brinda KV;Vishveshwara S
蛋白质-蛋白质缔合对于各种细胞过程是必不可少的，因此正在进行大量的研究以了解蛋白质-蛋白质相互作用的原理。在这项研究中，寡聚蛋白质结构被认为是从网络的角度来获得新的见解蛋白质协会。蛋白质的结构图已经从蛋白质寡聚体晶体结构的非冗余集合通过将氨基酸残基视为节点而构建，并且边缘基于残基之间的非共价相互作用的强度。这种网络的分析已经进行了氨基酸簇和枢纽（高度连接的残基），特别强调蛋白质接口。各种相互作用，如氢键，盐桥，芳族和疏水相互作用，这发生在接口被确定在一个统一的方式作为氨基酸簇在界面上，从这项研究。此外，在接口处的高度连接的枢纽形成残基的表征和它们与来自非接口区域的枢纽和在接口区域中的非枢纽的比较表明，在接口处存在占优势的带电相互作用。此外，强和弱接口的氨基酸残基之间的相互作用强度和接口集群的大小的基础上，这也表明，许多蛋白质的接口是强于它们的单体蛋白质的核心。基于界面簇和枢纽的界面强度评估也与已知复合物的实验测定的解离常数相关。最后，使用本方法确定的接口集线器非常好地与实验确定的热点从丙氨酸扫描能量学数据库（ASEdb）获得的蛋白质复合物的接口。根据分析结果，对界面热点进行了一些预测，有待实验验证。寡聚体蛋白质结构网络的构建和分析以及它们与单体蛋白质结构网络的比较为蛋白质缔合提供了见解。此外，使用本方法鉴定的界面枢纽可以是界面去稳定化突变的有效靶标。我们相信这种分析将大大提高我们对蛋白质缔合背后原理的认识，并有助于蛋白质设计。
Protein-protein association is essential for a variety of cellular processes and hence a large number of investigations are being carried out to understand the principles of protein-protein interactions. In this study, oligomeric protein structures are viewed from a network perspective to obtain new insights into protein association. Structure graphs of proteins have been constructed from a non-redundant set of protein oligomer crystal structures by considering amino acid residues as nodes and the edges are based on the strength of the non-covalent interactions between the residues. The analysis of such networks has been carried out in terms of amino acid clusters and hubs (highly connected residues) with special emphasis to protein interfaces. A variety of interactions such as hydrogen bond, salt bridges, aromatic and hydrophobic interactions, which occur at the interfaces are identified in a consolidated manner as amino acid clusters at the interface, from this study. Moreover, the characterization of the highly connected hub-forming residues at the interfaces and their comparison with the hubs from the non-interface regions and the non-hubs in the interface regions show that there is a predominance of charged interactions at the interfaces. Further, strong and weak interfaces are identified on the basis of the interaction strength between amino acid residues and the sizes of the interface clusters, which also show that many protein interfaces are stronger than their monomeric protein cores. The interface strengths evaluated based on the interface clusters and hubs also correlate well with experimentally determined dissociation constants for known complexes. Finally, the interface hubs identified using the present method correlate very well with experimentally determined hotspots in the interfaces of protein complexes obtained from the Alanine Scanning Energetics database (ASEdb). A few predictions of interface hot spots have also been made based on the results obtained from this analysis, which await experimental verification. The construction and analysis of oligomeric protein structure networks and their comparison with monomeric protein structure networks provide insights into protein association. Further, the interface hubs identified using the present method can be effective targets for interface de-stabilizing mutations. We believe this analysis will significantly enhance our knowledge of the principles behind protein association and also aid in protein design.
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影响因子：
5.6
作者：
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通讯作者：
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