Dynamic properties of a type II cadherin adhesive domain: implications for the mechanism of strand-swapping of classical cadherins.
Dynamic properties of a type II cadherin adhesive domain: implications for the mechanism of strand-swapping of classical cadherins.
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DOI：
10.1016/j.str.2008.05.009
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发表时间：
2008-08-06
期刊：
影响因子：
--
通讯作者：
Palmer AG 3rd
中科院分区：
文献类型：
--
作者：
Miloushev VZ;Bahna F;Ciatto C;Ahlsen G;Honig B;Shapiro L;Palmer AG 3rd
钙粘蛋白介导的细胞粘附是通过钙粘蛋白n端细胞外（EC1）结构域的二聚化实现的。二聚体状态是通过交换n端β链和将保守的色氨酸吲哚侧链从一个单体插入到伙伴分子的疏水受体口袋中形成的。本研究利用核磁共振光谱表征了小鼠II型钙粘蛋白-8 EC1结构域的单体和二聚体状态以及单体-二聚体平衡。色氨酸吲哚单体和二聚体状态的有限皮秒到纳秒时间尺度动力学分别与分子内和分子间n端β链的有序包装一致。然而，对于单体，而不是二聚体，可以观察到明显的微秒到毫秒的侧链时间尺度动力学，这表明单体的瞬态样品构型中吲哚部分暴露。低pH和钙的存在有利于二聚体的形成，表明钙在链交换机制中的作用。讨论了EC1二聚化的可能动力学机制。
Cadherin-mediated cell adhesion is achieved through dimerization of cadherin N-terminal extracellular (EC1) domains presented from apposed cells. The dimer state is formed by exchange of N-terminal β-strands and insertion of conserved tryptophan indole side chains from one monomer into hydrophobic acceptor pockets of the partner molecule. The present work characterizes individual monomer and dimer states and the monomer-dimer equilibrium of the mouse Type II cadherin-8 EC1 domain using NMR spectroscopy. Limited picosecond-to-nanosecond timescale dynamics of the tryptophan indole moieties for both monomer and dimer states are consistent with well-ordered packing of the N-terminal β-strands intramolecularly and intermolecularly, respectively. However, pronounced microsecond-to-millisecond timescale dynamics of the side chains are observed for the monomer, but not the dimer, state, suggesting that monomers transiently sample configurations in which the indole moieties are exposed. Dimer formation is favored at low pH and by the presence of calcium, indicating a role for calcium in the strand swapping mechanism. The results are discussed in terms of possible kinetic mechanisms for EC1 dimerization.
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影响因子：
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