Leckband Deborah
Department of Chemistry, Center for Biophysics and Computational Biology, University of Illinois, Urbana-Champaign, IL 61801, USA.
Biochem Soc Trans. 2008 Apr;36(Pt 2):213-20. doi: 10.1042/BST0360213.
This review summarizes findings from multiple complementary quantitative investigations of adhesion by classical cadherins. The systems investigated range from single molecules to cells, and the approaches used quantify the kinetics, energetics and mechanical strengths of cadherin bonds. The cumulative results demonstrate that cadherins adhere via a multistage binding mechanism that involves multiple extracellular domains. In kinetic measurements of cell adhesion, cell pairs first form a low-probability-binding state with fast kinetics. This is followed by a lag and a slow transition to a second, high-probability, binding state. This two-stage process is independent of the cytoplasmic domain. Studies with domain-deletion mutants demonstrate that the N-terminal domains are required for the first, fast, weak binding. However, the full-ectodomain and EC3 (extracellular repeat 3), in particular, are required to form the second, high-probability, binding state, which is characterized by slow dissociation kinetics and much stronger adhesive bonds. Together, these different studies reveal a more complex multistage binding mechanism than was predicted by structural models.
本综述总结了对经典钙黏着蛋白介导的黏附进行的多项互补定量研究的结果。所研究的系统涵盖从单分子到细胞，所采用的方法用于量化钙黏着蛋白键的动力学、能量学和机械强度。累积结果表明，钙黏着蛋白通过涉及多个细胞外结构域的多阶段结合机制实现黏附。在细胞黏附的动力学测量中，细胞对首先形成具有快速动力学的低概率结合状态。随后是一个延迟期以及向第二个高概率结合状态的缓慢转变。这个两阶段过程与细胞质结构域无关。对结构域缺失突变体的研究表明，N 端结构域是第一个快速、弱结合所必需的。然而，完整的胞外结构域，尤其是 EC3（细胞外重复序列 3），对于形成第二个高概率结合状态是必需的，该状态的特征是解离动力学缓慢且黏附键更强。总之，这些不同的研究揭示了一种比结构模型预测的更为复杂的多阶段结合机制。
