Institute for Biochemistry I, University Hospital Jena-Friedrich Schiller University Jena, Germany.
EMBO J. 2011 Aug 31;30(17):3501-15. doi: 10.1038/emboj.2011.266.
Against the odds of membrane resistance, members of the BIN/Amphiphysin/Rvs (BAR) domain superfamily shape membranes and their activity is indispensable for a plethora of life functions. While crystal structures of different BAR dimers advanced our understanding of membrane shaping by scaffolding and hydrophobic insertion mechanisms considerably, especially life-imaging techniques and loss-of-function studies of clathrin-mediated endocytosis with its gradually increasing curvature show that the initial idea that solely BAR domain curvatures determine their functions is oversimplified. Diagonal placing, lateral lipid-binding modes, additional lipid-binding modules, tilde shapes and formation of macromolecular lattices with different modes of organisation and arrangement increase versatility. A picture emerges, in which BAR domain proteins create macromolecular platforms, that recruit and connect different binding partners and ensure the connection and coordination of the different events during the endocytic process, such as membrane invagination, coat formation, actin nucleation, vesicle size control, fission, detachment and uncoating, in time and space, and may thereby offer mechanistic explanations for how coordination, directionality and effectiveness of a complex process with several steps and key players can be achieved.
尽管存在膜阻力，但 BIN/Amphiphysin/Rvs (BAR) 结构域超家族的成员能够塑造膜的形状，其活性对于多种生命功能是不可或缺的。尽管不同 BAR 二聚体的晶体结构通过支架和疏水性插入机制极大地促进了我们对膜重塑的理解，但生命成像技术和网格蛋白介导的内吞作用的功能丧失研究逐渐增加了曲率，表明最初认为仅仅 BAR 结构域曲率决定其功能的观点过于简单化。对角线放置、侧向脂质结合模式、额外的脂质结合模块、波浪形状以及不同组织和排列方式的大分子晶格的形成增加了多功能性。出现了这样的画面，BAR 结构域蛋白创建了大分子平台，招募和连接不同的结合伙伴，并确保在胞吞过程中不同事件的连接和协调，例如膜内陷、衣被形成、肌动蛋白成核、囊泡大小控制、分裂、脱离和去衣被，在时间和空间上，并为如何协调、定向和实现具有多个步骤和关键参与者的复杂过程的有效性提供了机制解释。
