Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 OQH, United Kingdom.
Proc Natl Acad Sci U S A. 2012 May 22;109(21):8127-32. doi: 10.1073/pnas.1120028109. Epub 2012 May 7.
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.
寡聚化在许多蛋白质的功能中起着重要作用。因此，理解、预测，最终设计寡聚化一直是人们关注的焦点。从结构生物学的角度来看，蛋白质-蛋白质相互作用主要是根据蛋白质界面的物理性质和进化来分析的。在这里，我们的目的是量化蛋白质界面的更大结构背景在蛋白质相互作用进化中的重要性。具体来说，我们想知道亚基间几何形状在多大程度上影响寡聚状态。我们定义了一组结构参数，用于描述具有不同寡聚状态的同源复合物的整体几何形状和相对位置。这使我们能够量化界面中直接序列变化与影响亚基间几何形状的界面外间接变化的贡献。我们发现，通过间接机制影响亚基间几何形状的这种间接或别构突变与界面序列变化一样，对寡聚状态的进化同样重要。
