Ando David, Zandi Roya, Kim Yong Woon, Colvin Michael, Rexach Michael, Gopinathan Ajay
Department of Physics, University of California at Merced, Merced, California.
Department of Physics, University of California at Riverside, Riverside, California.
Biophys J. 2014 May 6;106(9):1997-2007. doi: 10.1016/j.bpj.2014.03.021.
The transport of cargo across the nuclear membrane is highly selective and accomplished by a poorly understood mechanism involving hundreds of nucleoporins lining the inside of the nuclear pore complex (NPC). Currently, there is no clear picture of the overall structure formed by this collection of proteins within the pore, primarily due to their disordered nature. We perform coarse-grained simulations of both individual nucleoporins and grafted rings of nups mimicking the in vivo geometry of the NPC and supplement this with polymer brush modeling. Our results indicate that different regions or blocks of an individual NPC protein can have distinctly different forms of disorder and that this property appears to be a conserved functional feature. Furthermore, this block structure at the individual protein level is critical to the formation of a unique higher-order polymer brush architecture that can exist in distinct morphologies depending on the effective interaction energy between the phenylalanine glycine (FG) domains of different nups. Because the interactions between FG domains may be modulated by certain forms of transport factors, our results indicate that transitions between brush morphologies could play an important role in regulating transport across the NPC, suggesting novel forms of gated transport across membrane pores with wide biomimetic applicability.
货物穿过核膜的运输具有高度选择性，是通过一种尚不明确的机制完成的，该机制涉及排列在核孔复合体（NPC）内部的数百种核孔蛋白。目前，对于孔内这组蛋白质所形成的整体结构尚无清晰的认识，主要是因为它们具有无序的性质。我们对单个核孔蛋白以及模拟NPC体内几何形状的核孔蛋白嫁接环进行了粗粒度模拟，并通过聚合物刷建模进行补充。我们的结果表明，单个NPC蛋白的不同区域或片段可能具有截然不同的无序形式，并且这种特性似乎是一种保守的功能特征。此外，单个蛋白质水平上的这种片段结构对于形成独特的高阶聚合物刷结构至关重要，该结构可以根据不同核孔蛋白的苯丙氨酸 - 甘氨酸（FG）结构域之间的有效相互作用能以不同形态存在。由于FG结构域之间的相互作用可能会受到某些形式的转运因子的调节，我们的结果表明，刷形态之间的转变可能在调节穿过NPC的运输中起重要作用，这暗示了具有广泛仿生适用性的跨膜孔门控运输的新形式。
