Evolution of oligomeric state through geometric coupling of protein interfaces
Evolution of oligomeric state through geometric coupling of protein interfaces
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DOI：
10.1073/pnas.1120028109
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发表时间：
2012-05-22
影响因子：
11.1
通讯作者：
Teichmann, Sarah A.
中科院分区：
文献类型：
--
作者：
Perica, Tina;Chothia, Cyrus;Teichmann, Sarah A.
寡聚化在许多蛋白质的功能中发挥着重要作用。因此，理解，预测，并最终，工程寡聚化提出了一个长期的兴趣。从结构生物学的角度来看，蛋白质-蛋白质相互作用主要是从蛋白质界面的生物物理性质和进化方面进行分析的。在这里，我们的目标是量化蛋白质相互作用进化中蛋白质界面的更大结构背景的重要性。具体来说，我们问在何种程度上亚基间的几何形状影响寡聚状态。我们定义了一组结构参数描述的整体几何形状和相对位置的同聚配合物与不同的低聚状态的接口。这使我们能够量化的贡献，直接序列变化的接口与间接的变化外的接口，影响intersubunit几何。我们发现，这种间接的，或变构突变通过间接机制影响亚基间的几何结构是一样重要的低聚状态的演变接口序列的变化。
Oligomerization plays an important role in the function of many proteins. Thus, understanding, predicting, and, ultimately, engineering oligomerization presents a long-standing interest. From the perspective of structural biology, protein-protein interactions have mainly been analyzed in terms of the biophysical nature and evolution of protein interfaces. Here, our aim is to quantify the importance of the larger structural context of protein interfaces in protein interaction evolution. Specifically, we ask to what extent intersubunit geometry affects oligomerization state. We define a set of structural parameters describing the overall geometry and relative positions of interfaces of homomeric complexes with different oligomeric states. This allows us to quantify the contribution of direct sequence changes in interfaces versus indirect changes outside the interface that affect intersubunit geometry. We find that such indirect, or allosteric mutations affecting intersubunit geometry via indirect mechanisms are as important as interface sequence changes for evolution of oligomeric states.