Tamura K, Shan W S, Hendrickson W A, Colman D R, Shapiro L
Brookdale Center for Developmental and Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Neuron. 1998 Jun;20(6):1153-63. doi: 10.1016/s0896-6273(00)80496-1.
To investigate the possible biological function of the lateral "strand dimer" observed in crystal structures of a D1 domain extracellular fragment from N-cadherin, we have undertaken site-directed mutagenesis studies of this molecule. Mutation of most residues important in the strand dimer interface abolish the ability of N-cadherin to mediate cell adhesion. Mutation of an analogous central residue (Trp-2) in E-cadherin also abrogates the adhesive capacity of that molecule. We also determined the crystal structure of a Ca2+-complexed two-domain fragment from N-cadherin. This structure, like its E-cadherin counterpart, does not adopt the strand dimer conformation. This suggests the possibility that classical cadherins might stably exist in both dimeric and monomeric forms. Data from several laboratories imply that lateral dimerization or clustering of cadherins may increase their adhesivity. We suggest the possibility that the strand dimer may play a role in this activation.
为了研究在N-钙黏蛋白D1结构域细胞外片段晶体结构中观察到的侧向“链二聚体”的可能生物学功能，我们对该分子进行了定点诱变研究。链二聚体界面中大多数重要残基的突变消除了N-钙黏蛋白介导细胞黏附的能力。E-钙黏蛋白中类似的中心残基（Trp-2）的突变也消除了该分子的黏附能力。我们还确定了N-钙黏蛋白的一个Ca2+复合双结构域片段的晶体结构。该结构与其E-钙黏蛋白对应物一样，不采用链二聚体构象。这表明经典钙黏蛋白可能以二聚体和单体形式稳定存在。来自几个实验室的数据表明，钙黏蛋白的侧向二聚化或聚集可能会增加其黏附性。我们提出链二聚体可能在这种激活中起作用的可能性。
