Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, California 94158, USA.
Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York 10065, USA.
Nature. 2018 Mar 22;555(7697):475-482. doi: 10.1038/nature26003. Epub 2018 Mar 14.
Nuclear pore complexes play central roles as gatekeepers of RNA and protein transport between the cytoplasm and nucleoplasm. However, their large size and dynamic nature have impeded a full structural and functional elucidation. Here we determined the structure of the entire 552-protein nuclear pore complex of the yeast Saccharomyces cerevisiae at sub-nanometre precision by satisfying a wide range of data relating to the molecular arrangement of its constituents. The nuclear pore complex incorporates sturdy diagonal columns and connector cables attached to these columns, imbuing the structure with strength and flexibility. These cables also tie together all other elements of the nuclear pore complex, including membrane-interacting regions, outer rings and RNA-processing platforms. Inwardly directed anchors create a high density of transport factor-docking Phe-Gly repeats in the central channel, organized into distinct functional units. This integrative structure enables us to rationalize the architecture, transport mechanism and evolutionary origins of the nuclear pore complex.
核孔复合体作为细胞质和核质之间 RNA 和蛋白质运输的守门员，起着核心作用。然而，其庞大的尺寸和动态性质阻碍了对其结构和功能的全面阐明。在这里，我们通过满足与其组成部分的分子排列有关的广泛数据，以亚纳米精度确定了酵母酿酒酵母的整个 552 蛋白核孔复合体的结构。核孔复合体包含坚固的对角柱和连接到这些柱上的连接器电缆，为结构提供强度和灵活性。这些电缆还将核孔复合体的所有其他元件（包括与膜相互作用的区域、外环和 RNA 处理平台）联系在一起。向内定向的锚点在中央通道中形成了高浓度的运输因子停靠苯丙氨酸-甘氨酸重复序列，这些重复序列组织成不同的功能单元。这种综合结构使我们能够合理化核孔复合体的架构、运输机制和进化起源。
