Intermedilysin-Receptor Interactions during Assembly of the Pore Complex

Intermedilysin-Receptor Interactions during Assembly of the Pore Complex
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孔复合物组装过程中中间素-受体的相互作用

DOI:
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发表时间:
2009
影响因子:
4.8
通讯作者:
Eileen M. Hotze
Eileen M. Hotze
中科院分区:
生物学2区
文献类型:
--
作者:
Stephanie Lachapelle;R. Tweten;Eileen M. Hotze

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中间溶素(ILY)是胆固醇依赖性溶细胞素家族的一个不寻常的成员,因为它与人CD59(hCD59)结合,而不是直接与富含胆固醇的细胞膜结合。ILY与hCD59的结合引发毒素内的一系列构象变化,导致可溶性单体转化为寡聚膜嵌入的孔复合物。在这项研究中,ILY与其膜受体的协会已被检查整个组装和孔复合物的形成。使用在孔组装的各个阶段捕获的ILY突变体,我们显示ILY在整个prepore寡聚体的组装中保持与hCD59接合,但在转化为孔复合物时从受体脱离。我们进一步表明,组装中间体增加了宿主细胞对补体膜攻击复合物裂解的敏感性,显然是通过阻断补体蛋白C8α和C9的hCD59结合位点。
Intermedilysin (ILY) is an unusual member of the family of cholesterol-dependent cytolysins because it binds to human CD59 (hCD59) rather than directly to cholesterol-rich membranes. Binding of ILY to hCD59 initiates a series of conformational changes within the toxin that result in the conversion of the soluble monomer into an oligomeric membrane-embedded pore complex. In this study the association of ILY with its membrane receptor has been examined throughout the assembly and formation of the pore complex. Using ILY mutants trapped at various stages of pore assembly, we show ILY remains engaged with hCD59 throughout the assembly of the prepore oligomer, but it disengages from the receptor upon the conversion to the pore complex. We further show that the assembly intermediates increase the sensitivity of the host cell to lysis by its complement membrane attack complex, apparently by blocking the hCD59-binding site for complement proteins C8α and C9.
DOI: 10.1016/s0021-9258(18)98856-3
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