Prof. Michael P. Rout （米国ロックフェラー大学）
A Hole New View: Structure-Function Mapping of the Nuclear Pore Complex
Nuclear Pore Complexes (NPCs) mediate the transport of RNAs and proteins between the cytoplasm and nucleoplasm. We have recently determined a subnanometer precision structure for the entire 52 MDa, 552-protein yeast NPC by satisfying diverse data including stoichiometry, a cryo-electron tomography map, and chemical cross-links, revealing the NPC’s functional elements in unprecedented detail. The NPC is surprisingly modular, consisting of only 30 proteins of the nucleoporin family (Nups), which assemble into higher-order structures called spokes. Eight spokes assemble into even larger modules: coaxial outer and inner rings form a symmetric core scaffold, at the heart of which is found sturdy diagonal columns that act as keystones to the structure. The scaffold is connected to a membrane ring, a nuclear basket and cytoplasmic RNA export platform. Flexible connector cables hold these discrete and relatively rigid modules together, imbuing the scaffold with both strength and flexibility. The scaffold surrounds a central channel from which multiple intrinsically disordered Phe-Gly (FG) repeat motifs project, contributing to a central density termed the central transporter. These FG motifs mediate selective nucleocytoplasmic transport through specific interactions with nuclear transport factors. Taken together, this integrative structure allows us to rationalize the architecture and transport mechanism of the NPC.