Fernandez-Martinez Javier, Kim Seung Joong, Shi Yi, Upla Paula, Pellarin Riccardo, Gagnon Michael, Chemmama Ilan E, Wang Junjie, Nudelman Ilona, Zhang Wenzhu, Williams Rosemary, Rice William J, Stokes David L, Zenklusen Daniel, Chait Brian T, Sali Andrej, Rout Michael P
Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA.
Departments of Bioengineering and Therapeutic Sciences and Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell. 2016 Nov 17;167(5):1215-1228.e25. doi: 10.1016/j.cell.2016.10.028. Epub 2016 Nov 10.
The last steps in mRNA export and remodeling are performed by the Nup82 complex, a large conserved assembly at the cytoplasmic face of the nuclear pore complex (NPC). By integrating diverse structural data, we have determined the molecular architecture of the native Nup82 complex at subnanometer precision. The complex consists of two compositionally identical multiprotein subunits that adopt different configurations. The Nup82 complex fits into the NPC through the outer ring Nup84 complex. Our map shows that this entire 14-MDa Nup82-Nup84 complex assembly positions the cytoplasmic mRNA export factor docking sites and messenger ribonucleoprotein (mRNP) remodeling machinery right over the NPC's central channel rather than on distal cytoplasmic filaments, as previously supposed. We suggest that this configuration efficiently captures and remodels exporting mRNP particles immediately upon reaching the cytoplasmic side of the NPC.
mRNA 输出和重塑的最后步骤由 Nup82 复合体完成,它是核孔复合体(NPC)胞质面一个大型保守组件。通过整合各种结构数据,我们已在亚纳米精度上确定了天然 Nup82 复合体的分子结构。该复合体由两个组成相同但构型不同的多蛋白亚基组成。Nup82 复合体通过外环 Nup84 复合体嵌入 NPC。我们的图谱显示,这个完整的 14 兆达尔 Nup82 - Nup84 复合体组件将胞质 mRNA 输出因子停靠位点和信使核糖核蛋白(mRNP)重塑机制定位在 NPC 的中央通道上方,而不是像之前所认为的那样位于远端胞质细丝上。我们认为这种构型能够在输出的 mRNP 颗粒到达 NPC 胞质侧时立即有效地捕获并重塑它们。