Dynamics and stability of E-cadherin dimers
Dynamics and stability of E-cadherin dimers
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DOI：
10.1529/biophysj.106.087213
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发表时间：
2006-12-01
影响因子：
3.4
通讯作者：
Lavery, Richard
中科院分区：
文献类型：
--
作者：
Cailliez, Fabien;Lavery, Richard
钙粘蛋白的细胞外结构域在细胞粘附中起重要作用，尽管参与这一过程的结构尚不清楚。我们已经使用分子动力学来表征在E-钙粘蛋白晶体中鉴定的两个二聚体界面的构象和热力学性质，并且涉及两个最外的外域（EC 1和EC2）：涉及N-末端链交换的二聚体（称为“交换”二聚体）和涉及EC 1-EC2界面的“交错”二聚体。结果表明，交错的二聚体涉及一个小得多的界面面积，是明显低于交换二聚体的稳定性。还发现，尽管其稳定性，交换的二聚体经历了构象转变，导致更接近实验观察到的同源C-钙粘蛋白的结构。最后，将模拟的二聚体结构与E-、C-和N-钙粘蛋白的序列进行比较，显示交换的二聚体界面涉及令人惊讶的很少的在家族之间变化的残基，并且值得注意的是在E-和C-钙粘蛋白外域之间没有变化。
The extracellular domains of cadherins are known to play a major role in cell adhesion, although the structures involved in this process remain unclear. We have used molecular dynamics to characterize the conformational and thermodynamic properties of two of the dimer interfaces identified in E-cadherin crystals and involving the two outermost exodomains (EC1 and EC2): a dimer involving exchange of the N-terminal strand (referred to as the "swapped'' dimer) and a "staggered'' dimer involving an EC1-EC2 interface. The results show that the staggered dimer involves a much smaller interface area and is notably less stable than the swapped dimer. It is also found that, despite its stability, the swapped dimer undergoes a conformational transition leading to a structure closer to that experimentally observed for the homologous C-cadherin. Finally, comparing the simulated dimer structures with the sequences of E-, C-, and N-cadherins shows that the swapped dimer interface involves surprisingly few residues that vary from family to family and notably no changes between the E- and C- cadherin exodomains.