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人类衰变加速因子的分子建模与作用机制

Molecular modeling and mechanism of action of human decay-accelerating factor.

作者信息

Kuttner-Kondo L, Medof M E, Brodbeck W, Shoham M

机构信息

Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106-4935, USA.

出版信息

Protein Eng. 1996 Dec;9(12):1143-9. doi: 10.1093/protein/9.12.1143.

DOI:10.1093/protein/9.12.1143
PMID:9010927
Abstract

A model of the regulatory region of human decay accelerating factor (DAF) was built based on the known coordinates of a fragment of the structurally and functionally homologous serum protein, factor H. According to this model, the four short consensus repeats (SCRs) in DAF are arranged in a helical fashion. A positively charged surface area on SCRs 2 and 3, two of the three repeating units essential for function, is postulated to be the primary recognition site for the C3 convertases C4b2a and C3bBb. This area encompasses a cavity on SCR 2, as well as part of the groove on the SCR 2-SCR 3 interface. Two additional surface depressions are centered around the C-terminal disulfide bridges of SCRs 3 and 4. These are likely to provide additional ligand binding sites. Based on this model in conjunction with sequence homology to the Ba fragment of factor B, a mechanism of DAF's accelerated convertase decay action is postulated.

摘要

基于结构和功能同源的血清蛋白H因子片段的已知坐标,构建了人类衰变加速因子(DAF)调控区的模型。根据该模型,DAF中的四个短共有重复序列(SCR)呈螺旋状排列。SCR 2和SCR 3上带正电荷的表面积(这是三个功能必需的重复单元中的两个)被假定为C3转化酶C4b2a和C3bBb的主要识别位点。该区域包括SCR 2上的一个腔以及SCR 2 - SCR 3界面上凹槽的一部分。另外两个表面凹陷以SCR 3和SCR 4的C末端二硫键为中心。这些可能提供额外的配体结合位点。基于该模型并结合与B因子Ba片段的序列同源性,推测了DAF加速转化酶衰变作用的机制。

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