Molecular roots of degenerate specificity in syntenin's PDZ2 domain: Reassessment of the PDZ recognition paradigm
Molecular roots of degenerate specificity in syntenin's PDZ2 domain: Reassessment of the PDZ recognition paradigm
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DOI：
10.1016/s0969-2126(03)00125-4
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发表时间：
2003-07-01
期刊：
影响因子：
5.7
通讯作者：
Derewenda, ZS
中科院分区：
文献类型：
--
作者：
Kang, BS;Cooper, DR;Derewenda, ZS
支架蛋白 Syntenin 的 PDZ2 结构域的晶体结构（无论是未结合的还是与源自 IL5 受体（α 链）和 Synclecan 的 C 末端的肽形成复合物）揭示了 Syntenin 简并特异性的分子根源。三个不同的结合位点（S-0、S-1 和 S-2）对疏水性侧链具有亲和力，以组合方式发挥作用：S-1 和 S-2 共同作用以结合多聚糖，而 So 和 S-1 参与 IL5Rα 的结合。这两种相互作用模式均与先前的分类方案不一致，该分类方案将IL5Rα相互作用定义为I类(-S/T-X-phi)，将多聚糖相互作用定义为II类(-phi-X-phi)。这些结果与 PDZ 域的其他新兴结构数据相结合，要求对其分类及其机制的现有模型进行修订。
Crystal structures of the PDZ2 domain of the scaffolding protein syntenin, both unbound and in complexes with peptides derived from C termini of IL5 receptor (alpha chain) and synclecan, reveal the molecular roots of syntenin's degenerate specificity. Three distinct binding sites (S-0, S-1, and S-2), with affinities for hydrophobic side chains, function in a combinatorial way: S-1 and S-2 act together to bind syndecan, while So and S-1 are involved in the binding of IL5Ralpha. Neither mode of interaction is consistent with the prior classification scheme, which defined the IL5Ralpha interaction as class I (-S/T-X-phi) and the syndecan interaction as class II (-phi-X-phi). These results, in conjunction with other emerging structural data on PDZ domains, call for a revision of their classification and of the existing model of their mechanism.