Insights into the action of the superfamily of cholesterol-dependent cytolysins from studies of intermedilysin
Insights into the action of the superfamily of cholesterol-dependent cytolysins from studies of intermedilysin
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DOI：
10.1073/pnas.0403229101
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发表时间：
2005-01-18
影响因子：
11.1
通讯作者：
Parker, MW
中科院分区：
文献类型：
--
作者：
Polekhina, G;Giddings, KS;Parker, MW
胆固醇依赖性细胞溶素（CDCs）是一个超家族的成孔毒素，其特征是一个保守的非肽基序，被认为是通过胆固醇进行膜识别的关键。中间溶素（Intermedilysin， ILY）是一种不寻常的CDCs成员，对人类细胞具有特异性，并且在基序中含有非保守的取代。我们发现，ILY的细胞特异性是基于它与人类细胞特异性结合的能力，而不涉及CDC机制的其他一些特征。此外，ILY的细胞识别似乎仅在结构域4中编码，而不涉及ILY的变异非片段。我们证明了非包头颗粒参与了ILY的pre -to-pore转化，从而证明了非包头颗粒的结构与pre -to-pore转变之间的直接联系。我们已经确定了ILY的晶体结构，当与已知的原型CDC结构进行比较时，表明其3D结构的基本方面可能在所有CDC中都是保守的。
The cholesterol-dependent cytolysins (CDCs), a superfamily of pore-forming toxins, are characterized by a conserved unclecapeptide motif that is believed to be critical for membrane recognition by means of cholesterol. Intermedilysin (ILY), an unusual member of the CDCs, exhibits specificity for human cells and contains nonconservative substitutions in the motif. We show that the cellular specificity of ILY is based on its ability to specifically bind to human cells and does not involve some other feature of the CDC mechanism. Furthermore, cellular recognition by ILY appears to be encoded in domain 4 alone but does not involve the variant unclecapepticle of ILY. We show that the unclecapepticle is involved in the prepore-to-pore conversion of ILY and so demonstrate a direct connection between the structure of the unclecapepticle and the prepore-to-pore transition. We have determined the crystal structure of ILY, which, when compared to the known structure of a prototypical CDC, suggests that the basic aspects of its 3D structure are likely to be conserved in all CDCs.