Phase transitions in the assembly of multivalent signalling proteins.
Phase transitions in the assembly of multivalent signalling proteins.
复制标题
DOI：
10.1038/nature10879
复制
发表时间：
2012-03-07
期刊：
影响因子：
64.8
通讯作者：
Rosen, Michael K.
中科院分区：
文献类型：
--
作者：
Li, Pilong;Banjade, Sudeep;Cheng, Hui-Chun;Kim, Soyeon;Chen, Baoyu;Guo, Liang;Llaguno, Marc;Hollingsworth, Javoris V.;King, David S.;Banani, Salman F.;Russo, Paul S.;Jiang, Qiu-Xing;Nixon, B. Tracy;Rosen, Michael K.
细胞以从埃到微米的长度尺度组织。然而，埃尺度分子性质转化为微米尺度宏观性质的机制还没有很好的理解。在这里，我们表明，不同的，合成的多价大分子（包括多结构域蛋白质和RNA）之间的相互作用产生尖锐的，液-液分层相分离，在水溶液中产生微米级的液滴。这种宏观转变对应于小复合物和大的动态超分子聚合物之间的分子转变。相变所需的浓度与相互作用物种的价态直接相关。在肌动蛋白调节蛋白，神经元Wiskott-Aldrich综合征蛋白（N-WASP）与其建立的生物学伙伴Nck和磷酸化nephrin相互作用的情况下，相变对应于对肌动蛋白成核因子Arp 2/3复合物的活性急剧增加。这种转变受nephrin磷酸化程度的控制，这解释了系统的这种性质如何被激酶控制到调节效果。多价系统的广泛存在表明，相变可能用于空间组织和生物化学调节整个生物学的信息。
Cells are organized on length scales ranging from Angstroms to microns. However, the mechanisms by which Angstrom-scale molecular properties are translated to micron-scale macroscopic properties are not well understood. Here we show that interactions between diverse, synthetic multivalent macromolecules (including multi-domain proteins and RNA) produce sharp, liquid-liquid demixing phase separations, generating micron-sized liquid droplets in aqueous solution. This macroscopic transition corresponds to a molecular transition between small complexes and large, dynamic supramolecular polymers. The concentrations needed for phase transition are directly related to valency of the interacting species. In the case of the actin regulatory protein, neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) interacting with its established biological partners Nck and phosphorylated nephrin, the phase transition corresponds to a sharp increase in activity toward the actin nucleation factor, Arp2/3 complex. The transition is governed by the degree of phosphorylation of nephrin, explaining how this property of the system can be controlled to regulatory effect by kinases. The widespread occurrence of multivalent systems suggests that phase transitions are likely used to spatially organize and biochemically regulate information throughout biology.
登录
查看更多内容
影响因子：
3.8
作者：
Asherie, N;Pande, J;Benedek, GB
通讯作者：
Benedek, GB
影响因子：
5.5
作者：
Semenov, AN;Rubinstein, M
通讯作者：
Rubinstein, M
影响因子：
14.9
作者：
Obenauer, JC;Cantley, LC;Yaffe, MB
通讯作者：
Yaffe, MB
影响因子：
4.8
作者：
Dam, TK;Oscarson, S;Brewer, CF
通讯作者：
Brewer, CF
影响因子：
5.7
作者：
Chen, Baoyu;Doucleff, Michaeleen;Nixon, B. Tracy
通讯作者：
Nixon, B. Tracy