Soares Dinesh C, Gerloff Dietlind L, Syme Neil R, Coulson Andrew F W, Parkinson John, Barlow Paul N
Biocomputing Research Unit, Michael Swann Building, University of Edinburgh, The King's Buildings, Edinburgh EH9 3JJ, UK.
Protein Eng Des Sel. 2005 Aug;18(8):379-88. doi: 10.1093/protein/gzi039. Epub 2005 Jun 23.
Numerous mammalian proteins are constructed from a limited repertoire of module-types. Proteins belonging to the regulators of complement activation family--crucial for ensuring a complement-mediated immune response is targeted against infectious agents--are composed solely of complement control protein (CCP) modules. In the current study, CCP module sequences were grouped to allow selection of the most appropriate experimentally determined structures to serve as templates in an automated large-scale structure modelling procedure. The resulting 135 individual CCP module models, valuable in their own right, are available at the online database http://www.bru.ed.ac.uk/~dinesh/ccp-db.html. Comparisons of surface properties within a particular family of modules should be more informative than sequence alignments alone. A comparison of surface electrostatic features was undertaken for the first 28 CCP modules of complement receptor type 1 (CR1). Assignments to clusters based on surface properties differ from assignments to clusters based on sequences. This observation might reflect adaptive evolution of surface-exposed residues involved in protein-protein interactions. This illustrative example of a multiple surface-comparison was indeed able to pinpoint functional sites in CR1.
许多哺乳动物蛋白质是由有限种类的模块构建而成。属于补体激活调节因子家族的蛋白质——对于确保补体介导的免疫反应针对感染因子至关重要——仅由补体控制蛋白（CCP）模块组成。在当前研究中，CCP模块序列被分组，以便在自动化大规模结构建模过程中选择最合适的实验确定结构作为模板。由此产生的135个单独的CCP模块模型本身就很有价值，可在在线数据库http://www.bru.ed.ac.uk/~dinesh/ccp-db.html获取。特定模块家族内表面性质的比较应该比单独的序列比对更具信息性。对1型补体受体（CR1）的前28个CCP模块进行了表面静电特征比较。基于表面性质的聚类分配与基于序列的聚类分配不同。这一观察结果可能反映了参与蛋白质-蛋白质相互作用的表面暴露残基的适应性进化。这个多表面比较的示例确实能够确定CR1中的功能位点。
