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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 核孔复合物（NPC）是约50 MDa的蛋白质组装体，其选择性地运输货物穿过核膜。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学数据，并开发了一种使用这些数据定位NPC的456种组成蛋白的方法（见随附论文）。我们的结构揭示了NPC的一半是由核心支架组成的，这在结构上类似于囊泡涂层复合物。这种支架形成了一个交错的网络，覆盖了NPC嵌入其中的核膜的整个弯曲表面。运输的选择性屏障由大量蛋白质形成，这些蛋白质具有排列在支架内表面的无序区域。NPC仅由几个结构模块组成，这些模块在其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NPC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.