Mapping of putative binding sites on the ectodomain of the type II TGF-β receptor by scanning-deletion mutagenesis and knowledge-based modeling

Mapping of putative binding sites on the ectodomain of the type II TGF-β receptor by scanning-deletion mutagenesis and knowledge-based modeling
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DOI:
10.1016/s0014-5793(99)00869-8
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发表时间:
1999-07-30
期刊:
影响因子:
3.5
通讯作者:
O'Connor-McCourt, MD
O'Connor-McCourt, MD
中科院分区:
生物学3区
文献类型:
--
作者:
Guimond, A;Sulea, T;O'Connor-McCourt, MD

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II型转化生长因子(TGF)- β受体胞外结构域(T β RII-ECD)的结合表面通过结合扫描-删除突变结果和基于知识的外结构域结构建模来绘制。在T βⅱ- ecd核心结合域内产生的17个缺失突变体中,只有3个保留了与tgf - β的结合。基于激活素II型受体胞外结构域(ActRII-ECD)晶体结构的比较建模表明,在T β RII- ecd模型中,保留tgf - β结合的T β RII突变体在连接β链的一些环中被删除。在外域模型的结构框架内解释突变数据,可以预测T β ii - ecd表面的潜在结合位点。(C) 1999年欧洲生化学会联合会。
Binding surfaces of the type II transforming growth factor (TGF)-beta receptor extracellular domain (T beta RII-ECD) are mapped by combining scanning-deletion mutagenesis results with knowledge-based modeling of the ectodomain structure. Of the 17 deletion mutants produced within the core binding domain of T beta RII-ECD, only three retained binding to TGF-beta. Comparative modeling based on the crystal structure of the activin type II receptor extracellular domain (ActRII-ECD) indicates that the T beta RII mutants which retain TGF-beta binding are deleted in some of the loops connecting the beta-strands in the T beta RII-ECD model. Interpretation of the mutagenesis data within the structural framework of the ectodomain model allows for the prediction of potential binding sites at the surface of T beta RII-ECD. (C) 1999 Federation of European Biochemical Societies.