Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles.
Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles.
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DOI：
10.1016/j.molcel.2015.01.013
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发表时间：
2015-03-05
期刊：
影响因子：
16
通讯作者：
Baldwin, Andrew J.
中科院分区：
文献类型：
--
作者：
Nott, Timothy J.;Petsalaki, Evangelia;Farber, Patrick;Jervis, Dylan;Fussner, Eden;Plochowietz, Anne;Craggs, Timothy D.;Bazett-Jones, David P.;Pawson, Tony;Forman-Kay, Julie D.;Baldwin, Andrew J.
细胞将分子化学隔离在隔间，以促进和调节它们之间的相互作用。除了被膜包裹的隔室外，细胞还可以形成蛋白质质和无膜性细胞器，包括核仁、Cajal小体和PML小体，以及应激颗粒。决定这些结构形成时间和原因的原则仍然扑朔迷离。在这里，我们证明了Ddx4的无序尾巴，它是Nuage或生殖粒的主要成分，在活细胞和体外都形成了相分离的细胞器。这些小体由图案化的静电相互作用稳定，这些相互作用对温度、离子强度、精氨酸甲基化和剪接高度敏感。序列决定因素用于识别在无膜细胞器和细胞黏附中发现的蛋白质。此外，这些小体提供了另一种溶剂环境，可以浓缩单链DNA，但在很大程度上排除了双链DNA。我们认为，含有弱相互作用区块的无序蛋白质的相分离是形成受调节的无膜细胞器的一般机制。Ddx4的N末端在细胞内形成细胞器，在体外形成细胞器的相变是由静电相互作用驱动的，甲基化、离子强度和温度变化可以溶解细胞器序列，形成的决定因素在无膜细胞器蛋白Nott等人中是常见的。证明了在体外和细胞中，单一的蛋白质成分可以可逆地形成无膜细胞器。这些主体提供了一种替代的溶剂环境，可以浓缩单链DNA，但不包括双链DNA。我们认为，无序蛋白质的相分离是形成受调节的无膜细胞器的一般机制。
Cells chemically isolate molecules in compartments to both facilitate and regulate their interactions. In addition to membrane-encapsulated compartments, cells can form proteinaceous and membraneless organelles, including nucleoli, Cajal and PML bodies, and stress granules. The principles that determine when and why these structures form have remained elusive. Here, we demonstrate that the disordered tails of Ddx4, a primary constituent of nuage or germ granules, form phase-separated organelles both in live cells and in vitro. These bodies are stabilized by patterned electrostatic interactions that are highly sensitive to temperature, ionic strength, arginine methylation, and splicing. Sequence determinants are used to identify proteins found in both membraneless organelles and cell adhesion. Moreover, the bodies provide an alternative solvent environment that can concentrate single-stranded DNA but largely exclude double-stranded DNA. We propose that phase separation of disordered proteins containing weakly interacting blocks is a general mechanism for forming regulated, membraneless organelles. Intrinsically disordered N terminus of Ddx4 forms organelles in cells and in vitro Phase transition to form organelles is driven by electrostatic interactions Methylation, ionic strength, and temperature changes can dissolve the organelles Sequence determinants of formation are common in membraneless organelle proteins Nott et al. demonstrate that a single protein constituent can reversibly form membraneless organelles both in vitro and in cells. The bodies provide an alternative solvent environment that concentrates single-stranded, but exclude double-stranded DNA. We propose that phase separation of disordered proteins is a general mechanism for forming regulated, membraneless organelles.
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DOI：
10.1016/j.str.2013.08.001
发表时间：
2013-09-03
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Forman-Kay JD;Mittag T
通讯作者：
Mittag T
DOI：
10.1073/pnas.0911640106
发表时间：
2009-12-01
影响因子：
11.1
作者：
Chen, Chen;Jin, Jing;Pawson, Tony
通讯作者：
Pawson, Tony
影响因子：
56.9
作者：
Frey, Steffen;Richter, Ralf P.;Goerlich, Dirk
通讯作者：
Goerlich, Dirk
影响因子：
4
作者：
Hearst, Scoty M.;Gilder, Andrew S.;Hebert, Michael D.
通讯作者：
Hebert, Michael D.
影响因子：
3.4
作者：
Brangwynne, Clifford P.
通讯作者：
Brangwynne, Clifford P.