3 讨论 实验表明,作为微丝工具药物而广泛应用的鬼笔环肽可能对体外肌动蛋白大尺度聚合结构有较大的影响。在体外简单热力学体系中,肌动蛋白自组织为单纯的、无干预的热力学过程,完全受其内在的热力学特性所驱动。利用肌动蛋白聚合动力学的踏车模型可以较好地对肌动蛋白自组织行为进行定性的分析:在F-缓冲液中,肌动蛋白的聚合过程在经过成核期、生长期之后能够迅速进入动态平衡。此时,结合态的纤维型肌动蛋白残基与游离的球型肌动蛋白含量保持动态平衡。微丝的总体长度处于相对恒定的状态,受总长度的限制,单根微丝长度有限,微丝间的相互作用较难发生,形成交联的几率很小,因此在自组织过程中,肌动蛋白难以聚合形成连续的交联网络纤维结构,只能形成离散的纤维结构;在微丝稳定剂(如鬼笔环肽) 介入时,肌动蛋白聚合在经过成核期进入生长期之后,肌动蛋白体外自装配由于微丝解聚合过程被抑制而受到干预,正常的聚合P解聚合动态平衡受到破坏,导致自装配向聚合单方向进行,使溶液中的游离肌动蛋白和寡聚体浓度很低, 此时几乎所有的肌动蛋白均聚合为微丝,微丝的总长度接近最大,单根微丝相对较长,彼此之间的相互作用较易发生,因而容易形成大范围的交联网络结构。 Fig. 4 3D-reconstruction of two parallel filaments with different diameters. On the surface of the filaments , similar topological and conformational structure traits can be discerned ;suggesting that all the filaments observed in the experi-ment could result from the same thermodynamic process.The unit of scale ruler is nm.
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