A Bimodal Distribution of Two Distinct Categories of Intrinsically Disordered Structures with Separate Functions in FG Nucleoporins
A Bimodal Distribution of Two Distinct Categories of Intrinsically Disordered Structures with Separate Functions in FG Nucleoporins
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DOI：
10.1074/mcp.m000035-mcp201
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发表时间：
2010-10-01
影响因子：
7
通讯作者：
Rexach, Michael F.
中科院分区：
文献类型：
--
作者：
Yamada, Justin;Phillips, Joshua L.;Rexach, Michael F.
核孔复合体是真核生物核质运输的唯一通道。它们的门是由含有大的内在无序结构域的核孔蛋白形成的，这些结构域具有多个苯丙氨酸-甘氨酸重复序列(FG结构域)。结合起来，这些被认为是在NPC中心形成一个结构和化学上均一的随机卷曲网络，根据大小和疏水性对大分子进行分类。相反，我们发现FG结构域在结构和化学上是异质的。它们在非随机分布中采用了不同类别的内在无序结构。有些采用球状、折叠线圈结构，具有电荷含量低的特点。其他的则是高度带电的，采用更动态的、延长的线圈构型。有趣的是，几个FG核孔蛋白具有这两种结构的特征，沿着其多肽链呈双峰分布。这种分布在功能上与它们与显示相互粘合的折叠线圈FG结构域和显示排斥的扩展线圈FG结构域相互作用的吸引力或排斥性相关。从拓扑上看，这些两部分FG结构域可能类似于连接到松弛或延伸的线圈尖端的粘性熔融球体。在NPC内部，FG核孔蛋白的拥挤及其基于其拓扑、尺寸和内聚性的无序结构的分离可能迫使FG结构域在NPC中心形成管状门结构或转运体，具有两个独立的具有不同物理化学性质的交通区。分子与细胞蛋白质组学9：2205-2224,2010。
Nuclear pore complexes (NPCs) gate the only conduits for nucleocytoplasmic transport in eukaryotes. Their gate is formed by nucleoporins containing large intrinsically disordered domains with multiple phenylalanine-glycine repeats (FG domains). In combination, these are hypothesized to form a structurally and chemically homogeneous network of random coils at the NPC center, which sorts macromolecules by size and hydrophobicity. Instead, we found that FG domains are structurally and chemically heterogeneous. They adopt distinct categories of intrinsically disordered structures in non-random distributions. Some adopt globular, collapsed coil configurations and are characterized by a low charge content. Others are highly charged and adopt more dynamic, extended coil conformations. Interestingly, several FG nucleoporins feature both types of structures in a bimodal distribution along their polypeptide chain. This distribution functionally correlates with the attractive or repulsive character of their interactions with collapsed coil FG domains displaying cohesion toward one another and extended coil FG domains displaying repulsion. Topologically, these bipartite FG domains may resemble sticky molten globules connected to the tip of relaxed or extended coils. Within the NPC, the crowding of FG nucleoporins and the segregation of their disordered structures based on their topology, dimensions, and cohesive character could force the FG domains to form a tubular gate structure or transporter at the NPC center featuring two separate zones of traffic with distinct physicochemical properties. Molecular & Cellular Proteomics 9:2205-2224, 2010.