Defining the CD59-C9 binding interaction
Defining the CD59-C9 binding interaction
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DOI：
10.1074/jbc.m603690200
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发表时间：
2006-09-15
影响因子：
4.8
通讯作者：
Tomlinson, Stephen
中科院分区：
文献类型：
--
作者：
Huang, Yuxiang;Qiao, Fei;Tomlinson, Stephen
CD59是一种膜糖蛋白，调节宿主细胞膜上溶细胞膜攻击复合体(MAC或C5b-9)的形成。它通过在MAC组装过程中结构重排后与C8(阿尔法链)和C9结合来发挥作用。以往的研究表明，C9的CD59结合位点位于25个残基的二硫键环内，而C8的α位于与C9的CD59结合区重叠的51个残基序列中。通过肽筛选以及在结合分析、功能分析、计算机模拟和对接研究中使用肽，我们已经确定人类C9的6个残基序列，跨越365-371个残基，是参与CD59介导的MAC形成调节的主要CD59识别结构域。数据还表明，C8α和C9都与CD59上的一个相似或重叠的位点结合。此外，CD59-多肽对接模型的数据与CD59上位于疏水口袋的C9结合位点一致，这可能是先前通过CD59突变和建模研究确定的。
CD59 is a membrane glycoprotein that regulates formation of the cytolytic membrane attack complex(MAC or C5b-9) on host cell membranes. It functions by binding to C8 (alpha chain) and C9 after their structural rearrangement during MAC assembly. Previous studies indicated that the CD59 binding site in C9 was located within a 25-residue disulfide-bonded loop, and in C8 alpha was located within a 51-residue sequence that overlaps the CD59 binding region of C9. By peptide screens and the use of peptides in binding assays, functional assays, and computer modeling and docking studies, we have identified a 6-residue sequence of human C9, spanning residues 365-371, as the primary CD59 recognition domain involved in CD59-mediated regulation of MAC formation. The data also indicate that both C8 alpha and C9 bind to a similar or overlapping site on CD59. Furthermore, data from CD59-peptide docking models are consistent with the C9 binding site on CD59 located at a hydrophobic pocket, putatively identified previously by CD59 mutational and modeling studies.