用原子力显微镜测量Mac-1和ICAM-1单分子相互作用力

发布时间：2018-02-20 20:58

本文关键词： Mac-1 ICAM-1 AFM 单分子成键几率动力学力谱　出处：《第二军医大学》2007年硕士论文　论文类型：学位论文

【摘要】： Mac-1属于β2整合素家族,是位于白细胞表面的参与机体防御作用及免疫反应极为重要的粘附分子,在神经系统的小胶质细胞和巨噬细胞上也有表达,参与脱髓鞘病变过程中的髓鞘吞噬。ICAM-1属于免疫球蛋白超家族,位于血管内皮细胞上,是Mac-1的主要配体。两者的相互作用在白细胞与内皮细胞的牢固粘附中起非常重要的作用。Mac-1有一个重要的特点那就是对配体的粘附能力是受动态调节的,只有受到刺激被激活时才会对它的各种配体表现出高的粘附能力。然而到目前为止对于Mac-1活化后究竟是怎样导致对配体粘附能力增高的,其本质到底如何还没有相关研究。本课题利用原子力显微镜对Mac-1和其配体ICAM-1间的相互作用进行了直接的测量,结果显示Mac-1被活化后,与ICAM-1的结合几率增高,结合力增大。通过比较ICAM-1与活化的Mac-1及不同Mac-1突变体之间的动力学力谱,我们推测I结构域α7螺旋的下移是Mac-1活化的关键步骤。
[Abstract]:Mac-1 belongs to the 尾 2 integrin family and is an important adhesion molecule on the surface of leukocytes involved in defense and immune response. It is also expressed in microglia and macrophages of the nervous system. The phagocytosis of myelin sheath. ICAM-1, which is involved in demyelinating lesions, belongs to the immunoglobulin superfamily and is located on vascular endothelial cells. It is the main ligand of Mac-1. The interaction between them plays a very important role in the solid adhesion of leukocyte to endothelial cells. Mac-1 has an important characteristic that the adhesion ability to the ligand is dynamically regulated. Only when activated by stimuli do they exhibit high adhesion to its ligands. However, how has the activation of Mac-1 led to increased adhesion to ligands so far? In this study, the interaction between Mac-1 and its ligand ICAM-1 was measured by atomic force microscope. The results showed that the binding probability of Mac-1 to ICAM-1 was increased when Mac-1 was activated. By comparing the kinetic force spectra of ICAM-1 with activated Mac-1 and different Mac-1 mutants, we speculate that the downward shift of 伪 7 helix in I domain is the key step of Mac-1 activation.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R392

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