Electrostatic complementarity at protein/protein interfaces
Electrostatic complementarity at protein/protein interfaces
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DOI：
10.1006/jmbi.1997.0987
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发表时间：
1997-05-02
影响因子：
5.6
通讯作者：
Colman, PM
中科院分区：
文献类型：
--
作者：
McCoy, AJ;Epa, VC;Colman, PM
对蛋白质-蛋白质复合物的静电电位的计算得出了蛋白质-蛋白质界面显示“电荷互补性”和“静电互补性”的一般断言。在这项研究中，这两个术语的定量测量被开发出来，并用于严格地研究蛋白质-蛋白质界面。电荷互补性（CC）是用界面上最近邻原子上电荷的相关性来定义的。所有12个蛋白质界面的CC值都很小。因此，电荷互补性一词在CC测量的意义上并不适合描述蛋白质-蛋白质界面，静电互补性（EC）是通过蛋白质-蛋白质界面表面静电势的相关性来定义的。所有12个被研究的蛋白质-蛋白质界面都有显著的EC值，因此，蛋白质-蛋白质结合涉及具有互补静电势的表面的断言基本上得到了证实。因此，术语静电互补性可以用来描述蛋白质-蛋白质界面时，使用意义上的测量EC。综上所述，CC和EC的结果证明了电荷的远程效应的相关性，正如在结合界面上的静电势所描述的那样。EC值并没有像测量蛋白质-蛋白质界面的几何互补性那样，按照抗原-抗体和蛋白酶抑制剂等类型来划分复合物。EC值也与界面中盐桥的数量没有直接关系，这些盐桥的中和表明，其他电荷也对蛋白质之间的静电互补和静电相互作用有显著贡献。将EC定义的静电互补性扩展到研究流感病毒神经氨酸酶两种单克隆抗体NC10和NC41表位重叠处的静电相似性，尽管NC10和NC41与神经氨酸酶的相互作用都具有相当高的EC值，但两者在表位重叠区域产生的静电电位的相似性不显著。因此，两种抗体以不同的方式识别蛋白质的静电表面是可能的。(C) 1997学术出版社有限公司
Calculation of the electrostatic potential of protein-protein complexes has led to the general assertion that protein-protein interfaces display ''charge complementarity'' and ''electrostatic complementarity''. In this study, quantitative measures for these two terms are developed and used to investigate protein-protein interfaces in a rigorous manner. Charge complementarity (CC) was defined using the correlation of charges on nearest neighbour atoms at the interface. All 12 protein-protein interfaces studied had insignificantly small CC values. Therefore, the term charge complementarity is not appropriate for the description of protein-protein interfaces when used in the sense measured by CC. Electrostatic complementarity (EC) was defined using the correlation of surface electrostatic potential at protein-protein interfaces. All twelve protein-protein interfaces studied had significant EC values, and thus the assertion that protein-protein association involves surfaces with complementary electrostatic potential was substantially confirmed. The term electrostatic complementarity can therefore be used to describe protein-protein interfaces when used sense measured by EC. Taken together, the results for CC and EC demonstrate the relevance of the long-range effects of charges, as described by the electrostatic potential at the binding interface. The EC value did not partition the complexes by type such as antigen-antibody and proteinase-inhibitor, as measures of the geometrical complementarity at protein-protein interfaces have done. The EC value was also not directly related to the number of salt bridges in the interface, and neutralisation of these salt bridges showed that other charges also contributed significantly to electrostatic complementarity and electrostatic interactions between the proteins. Electrostatic complementarity as defined by EC was extended to investigate the electrostatic similarity at the surface of influenza virus neuraminidase where the epitopes of two monoclonal antibodies, NC10 and NC41, overlap, Although NC10 and NC41 both have quite high values of EC for their interaction with neuraminidase, the similarity in electrostatic potential generated by the two on the overlapping region of the epitopes is insignificant. Thus, it is possible for two antibodies to recognise the electrostatic surface of a protein in dissimilar ways. (C) 1997 Academic Press Limited.