Cargo modulates the conformation of the nuclear pore in living cells

While the static structure of the nuclear pore complex (NPC) continues to be refined with cryo-EM and x-ray crystallography, the in vivo conformational dynamics of the NPC remain under-explored. We developed sensors that report on the orientation of NPC components by rigidly conjugating mEGFP to different NPC proteins. Our studies show conformational changes to select domains of Nups within the inner ring (Nup54, Nup58, Nup62) when transport through the NPC is perturbed and no conformational changes to Nups elsewhere in the NPC. Our results suggest that select components of the NPC are flexible and undergo conformational changes upon engaging with cargo.