Mutations at protein-protein interfaces: Small changes over big surfaces have large impacts on human health
Mutations at protein-protein interfaces: Small changes over big surfaces have large impacts on human health
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DOI：
10.1016/j.pbiomolbio.2016.10.002
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发表时间：
2017-09-01
影响因子：
3.8
通讯作者：
Ascher, David B.
中科院分区：
文献类型：
--
作者：
Jubb, Harry C.;Pandurangan, Arun P.;Ascher, David B.
许多重要的生物学过程，包括细胞调节和信号传导是通过蛋白质复合物的组装介导的。蛋白质-蛋白质相互作用（PPI）界面的变化可以影响多蛋白复合物的形成，从而导致细胞内和细胞间PPI互连网络的破坏，进一步导致表型变化，因为功能相互作用被创建或破坏。改变PPI的突变与遗传疾病（包括癌症和罕见的孟德尔疾病）的发展以及耐药性的发展有关。这些蛋白质突变的重要性导致了许多资源的开发，以了解和预测其影响。我们认为，更好地了解这些突变如何影响多蛋白复合物的结构、功能和形成，为解决这些问题提供了新的机会，包括开发专门针对突变PPI的小分子药物。(C)2016作者爱思唯尔有限公司出版
Many essential biological processes including cell regulation and signalling are mediated through the assembly of protein complexes. Changes to protein-protein interaction (PPI) interfaces can affect the formation of multiprotein complexes, and consequently lead to disruptions in interconnected networks of PPIs within and between cells, further leading to phenotypic changes as functional interactions are created or disrupted. Mutations altering PPIs have been linked to the development of genetic diseases including cancer and rare Mendelian diseases, and to the development of drug resistance. The importance of these protein mutations has led to the development of many resources for understanding and predicting their effects. We propose that a better understanding of how these mutations affect the structure, function, and formation of multiprotein complexes provides novel opportunities for tackling them, including the development of small-molecule drugs targeted specifically to mutated PPIs. (C) 2016 The Authors. Published by Elsevier Ltd.