Formation of nNOS/PSD-95 PDZ dimer requires a preformed β-finger structure from the nNOS PDZ domain
Formation of nNOS/PSD-95 PDZ dimer requires a preformed β-finger structure from the nNOS PDZ domain
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DOI：
10.1006/jmbi.2000.4148
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发表时间：
2000-10-27
影响因子：
5.6
通讯作者：
Zhang, MJ
中科院分区：
文献类型：
--
作者：
Tochio, H;Mok, YK;Zhang, MJ
PDZ结构域是在组织信号转导复合物中发挥重要作用的模块化蛋白质单位。PDZ结构域介导与C-末端肽配体和其他PDZ结构域的相互作用。在这里，我们使用PDZ结构域从神经元型一氧化氮合酶（nNOS）和突触后密度蛋白-95（PSD-95），以探讨PDZ-二聚体形成的机制。nNOS PDZ结构域以类似于30个氨基酸残基的β-指肽终止，所述β-指肽显示为nNOS/PSD-95 PDZ二聚体形成所需的。此外，PDZ二聚体的形成需要该β-指肽物理锚定到典型nNOS PDZ结构域的主体上.β-指和PDZ结构域之间的埋藏盐桥诱导并稳定nNOSDZ结构域的β-发夹结构.在apo-nNOS中，β-指肽是部分柔性的，并且采用在PDZ二聚体形成时稳定的瞬时β-链样结构。NOS PDZ β-指的柔性可能在支持nNOS/PSD-95复合物的形成中起关键作用。实验数据还表明，nNOS PDZ和PSD-95的第二PDZ结构域形成类似于通过X射线晶体学表征的nNOS/促突触蛋白复合物的“头-尾”二聚体。(C)北京大学出版社.
PDZ domains are modular protein units that play important roles in organizing signal transduction complexes. PDZ domains mediate interactions with both C-terminal peptide ligands and other PDZ domains. Here, we used PDZ domains from neuronal nitric oxide synthase (nNOS) and postsynaptic density protein-95 (PSD-95) to explore the mechanism for PDZ-dimer formation. The nNOS PDZ domain terminates with a similar to 30 residue amino acid beta -finger peptide that is shown to be required for nNOS/PSD-95 PDZ dimer formation. Ln addition, formation of the PDZ dimer requires this beta -finger peptide to be physically anchored to the main body of the canonical nNOS PDZ domain. A buried salt bridge between the beta -finger and the PDZ domain induces and stabilizes the beta -hairpin structure of the nNOS PDZ domain. In apo-nNOS, the beta -finger peptide is partially flexible and adopts a transient beta -strand like structure that is stabilized upon PDZ dimer formation. The flexibility of the NOS PDZ beta -finger is likely to play a critical role in supporting the formation of nNOS/PSD-95 complex. The experimental data also suggest that nNOS PDZ and the second PDZ domain of PSD-95 form a "head-to-tail" dimer similar to the nNOS/syntrophin complex characterized by X-ray crystallography. (C) 2000 Academic Press.