The molecular architecture of cadherins in native epidermal desmosomes
The molecular architecture of cadherins in native epidermal desmosomes
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DOI：
10.1038/nature05994
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发表时间：
2007-12-06
期刊：
影响因子：
64.8
通讯作者：
Frangakis, Achilleas S.
中科院分区：
文献类型：
--
作者：
Al-Amoudi, Ashraf;Diez, Daniel Castano;Frangakis, Achilleas S.
桥粒是基于钙粘蛋白的黏附细胞间连接点，存在于心脏和皮肤等组织中。尽管付出了相当大的努力，介导粘附的分子界面仍然不清楚。在这里，我们应用人体表皮玻璃体切片的低温电子断层扫描来可视化在接近天然条件下桥粒钙粘蛋白的三维分子结构。三维重建显示沿中线有规则的密度阵列，密度间隔约为70埃，具有弯曲形状，类似于典型的“经典”钙粘蛋白C- cadherin的X射线结构。对提取的亚层析图进行独立于模型的三维图像处理，揭示了钙粘蛋白的组织结构。在将C-钙粘蛋白原子结构拟合到平均亚断层图中后，我们看到了反式W-样和顺式V-样相互作用的周期性排列，分别对应于来自对立膜和同一细胞膜的分子。由此产生的钙粘蛋白组织模型解释了现有的二维数据，并对基于钙粘蛋白的细胞粘附的可能机制产生了见解。
Desmosomes are cadherin- based adhesive intercellular junctions, which are present in tissues such as heart and skin. Despite considerable efforts, the molecular interfaces that mediate adhesion remain obscure. Here we apply cryo- electron tomography of vitreous sections from human epidermis to visualize the three- dimensional molecular architecture of desmosomal cadherins at close- to- native conditions. The three- dimensional reconstructions show a regular array of densities at similar to 70 angstrom intervals along the midline, with a curved shape resembling the X- ray structure of C- cadherin, a representative 'classical' cadherin. Model- independent three- dimensional image processing of extracted sub- tomograms reveals the cadherin organization. After fitting the C- cadherin atomic structure into the averaged sub- tomograms, we see a periodic arrangement of a trans W- like and a cis V- like interaction corresponding to molecules from opposing membranes and the same cell membrane, respectively. The resulting model of cadherin organization explains existing two- dimensional data and yields insights into a possible mechanism of cadherin- based cell adhesion.