Membrane fission is promoted by insertion of amphipathic helices and is restricted by crescent BAR domains.
Membrane fission is promoted by insertion of amphipathic helices and is restricted by crescent BAR domains.
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DOI：
10.1016/j.cell.2012.01.047
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发表时间：
2012-03-30
期刊：
影响因子：
64.5
通讯作者：
Kozlov MM
中科院分区：
文献类型：
--
作者：
Boucrot E;Pick A;Çamdere G;Liska N;Evergren E;McMahon HT;Kozlov MM
浅的疏水插入和新月形BAR支架促进膜弯曲。在这里，我们调查膜裂变的浅疏水插入定量和机械。我们提供的证据表明，膜插入的ENTH结构域的epsin导致脂质体囊泡形成，和epsin是网格蛋白包被的囊泡在细胞中出芽所需的。我们还表明，来自内嗜蛋白、两性啡肽、GRAF和β2-centaurin的BAR结构域支架限制了由疏水插入驱动的膜分裂。囊泡形成的定量分析揭示了分裂中两亲性螺旋和N-BAR结构域支架之间的拮抗关系。这些蛋白质的囊泡化程度和囊泡大小取决于每个BAR结构域的两亲性螺旋的数量和长度，这与理论考虑雅阁。这种裂变机制提供了一个新的框架，了解膜断裂的机械酶，如发动蛋白的情况下，并建议Arf和SAR蛋白如何在囊泡断裂工作。膜蛋白包被的囊泡的断裂需要Epsin的参与。由浅疏水插入引起的曲率导致膜分裂。BAR-domain新月形支架抑制膜分裂。定量囊泡形成分析显示支架和插入之间的竞争。这种反应受到BAR结构域的限制，BAR结构域通常存在于具有两亲性螺旋的相同蛋白质中，这表明在体内膜囊泡化的倾向可以通过与蛋白质结构域相关的组合效应来调节。
Shallow hydrophobic insertions and crescent-shaped BAR scaffolds promote membrane curvature. Here, we investigate membrane fission by shallow hydrophobic insertions quantitatively and mechanistically. We provide evidence that membrane insertion of the ENTH domain of epsin leads to liposome vesiculation, and that epsin is required for clathrin-coated vesicle budding in cells. We also show that BAR-domain scaffolds from endophilin, amphiphysin, GRAF, and β2-centaurin limit membrane fission driven by hydrophobic insertions. A quantitative assay for vesiculation reveals an antagonistic relationship between amphipathic helices and scaffolds of N-BAR domains in fission. The extent of vesiculation by these proteins and vesicle size depend on the number and length of amphipathic helices per BAR domain, in accord with theoretical considerations. This fission mechanism gives a new framework for understanding membrane scission in the absence of mechanoenzymes such as dynamin and suggests how Arf and Sar proteins work in vesicle scission. ► Epsin is required for clathrin-coated vesicle scission ► Curvature induced by shallow hydrophobic insertions leads to membrane fission ► BAR-domain crescent scaffolds restrain membrane fission ► Quantitative vesiculation assay shows competition between scaffolds and insertions Shallow hydrophobic deformations of a membrane by amphipathic helices not only cause changes in curvature but also drive complete fission. This reaction is limited by BAR domains that are often found in the same proteins with amphipathic helices, suggesting that in vivo the propensity for a membrane to vesiculate can be regulated by a combinatory effect associated with protein domains.
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DOI：
10.1038/nrm2937
发表时间：
2010-08
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.0710267105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Jakobsson, Joel;Gad, Helge;Brodin, Lennart
通讯作者：
Brodin, Lennart
影响因子：
64.5
作者：
Lee, MCS;Orci, L;Schekman, R
通讯作者：
Schekman, R
DOI：
10.1073/pnas.0907008106
发表时间：
2009-08-18
影响因子：
11.1
作者：
Chen, Hong;Ko, Genevieve;Cremona, Ottavio
通讯作者：
Cremona, Ottavio
影响因子：
--
作者：
Coon, Brian G;Direnzo, Daniel M;Aguilar, R Claudio
通讯作者：
Aguilar, R Claudio