The Nuclear Pore Basket – Functional Architecture of a Membrane Remodeling Machine

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Nuclear pore complexes (NPCs) are gatekeepers at the nuclear envelope, mediating traffic between the nucleus and cytoplasm. Unlike simpler protein channels that insert into a single lipid bilayer, NPCs can remodel the outer and inner nuclear membranes to form a specialized pore in the nuclear envelope. High-resolution models of the symmetric NPC core have transformed our understanding of NPC architecture. In contrast, we know little about the NPC basket, a prominent structure on the nucleoplasmic side of NPCs. This lack of knowledge is salient, because the basket impacts on transport, DNA repair, and chromatin activity. Notably, the basket was recently found to play a key role in shaping the nuclear membrane, which is critical for NPC biogenesis. Studying the NPC basket is challenging because of its size, intricate architecture, structural flexibility and embedding in a membrane. Yet, knowledge of the architecture of the NPC basket is central to understanding how it influences gene expression, and operates in membrane remodeling in synergy with the NPC core. I propose to develop new experimental tools that will enable a structural analysis of the basket in its membrane environment. This will provide unprecedented insight into the function of this enigmatic part of the NPC.