MOLECULAR ARCHITECTURE OF NUCLEAR PORE COMPLEX (NPC) FROM YEAST S CEREVISIAE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 核孔复合体(NPC)是由大约50个丙二醛组成的蛋白质集合体，选择性地将货物运输到核膜上。为了确定酵母NPC的分子结构，我们收集了一组不同的生物物理和蛋白质组数据，并开发了一种使用这些数据来定位NPC的456个组成蛋白质的方法(见随附的论文)。我们的结构表明，NPC的一半由核心支架组成，其结构类似于囊泡涂层复合体。这种支架形成了一个交错的网络，覆盖了嵌入NPC的核包膜的整个曲面。运输的选择性屏障是由大量蛋白质形成的，这些蛋白质的无序区域排列在支架的内表面。NPC只由几个结构模块组成，这些模块在同源成分的配置方面彼此相似，其中最引人注目的是16倍重复的“柱”。这些发现为鼻咽癌的进化起源提供了线索。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Nuclear pore complexes (NPCs) are proteinaceous assemblies of approximately 50 MDa that selectively transport cargoes across the nuclear envelope. To determine the molecular architecture of the yeast NPC, we collected a diverse set of biophysical and proteomic data, and developed a method for using these data to localize the NPC's 456 constituent proteins (see the accompanying paper). Our structure reveals that half of the NPC is made up of a core scaffold, which is structurally analogous to vesicle-coating complexes. This scaffold forms an interlaced network that coats the entire curved surface of the nuclear envelope membrane within which the NPC is embedded. The selective barrier for transport is formed by large numbers of proteins with disordered regions that line the inner face of the scaffold. The NPC consists of only a few structural modules that resemble each other in terms of the configuration of their homologous constituents, the most striking of these being a 16-fold repetition of 'columns'. These findings provide clues to the evolutionary origins of the NPC.