一个大规模的形状变化伴侣膜招募到货物结合在AP2克拉林适配器复合体的载荷结合
Lauren P Jackson1, Bernard T Kelly, Airlie J McCoy
1Cambridge Institute for Medical Research, Department of Clinical Biochemistry, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Cell
|July 7, 2010
概括
AP2适配器复合体经历了结构变化,解锁了货物结合点. 这种结构性转变促进了AP2的发展.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- AP2适配器复合体对于克拉林介导的内细胞形成至关重要.
- AP2通过含有PtdIns4,5P(2) 的膜将跨膜货物连接到克拉特林支架上.
- 在细胞质形式下,AP2的载荷结合部位被β2亚单元阻断.
研究的目的:
- 阐明AP2激活的结构机制.
- 了解AP2如何从"锁定"状态过渡到"开放"状态以进行货物绑定.
- 调查PtdIns4,5P(2) 在AP2介导的内细胞分裂中的作用.
主要方法:
- 蛋白质结晶学被用来确定AP2的结构.
- 生物物理技术被用来研究AP2-膜相互作用.
- 分析了AP2子单位的合规变化.
主要成果:
- AP2经历了显著的构造变化,将mu2 (C-mu2) 的C终端域重新定位.
- 这种重新排列解锁了YxxPhi和[ED]xxxL[LI]内细胞动机结合部位.
- 四个PtdIns4,5P(2) 结合点和两个货物结合点成为共平面.
- AP2与含有PtdIns4,5P(2) 的膜的相互作用驱动了内细胞载荷结合.
结论:
- AP2的形状灵活性对于其在内细胞分裂中的功能至关重要.
- 同时结合PtdIns4,5P(2) 和货物图案是通过结合点的共平面布局来促进的.
- 与PtdIns4,5P(2) 的膜相互作用是AP2内细胞载荷招募的主要驱动因素.
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