Dissecting the Structural Dynamics of the Nuclear Pore Complex

Cellular processes are largely carried out by macromolecular assemblies, most of which are dynamic, having components that are in constant flux. One such assembly is the nuclear pore complex (NPC), a ~50 MDa assembly comprised of ~30 different proteins termed Nups that mediates selective macromolecular transport between the nucleus and cytoplasm. We have developed a proteomic method to provide a comprehensive picture of the yeast NPC’s component dynamics. We discovered that while all Nups display a uniformly slow turnover, their exchange rates vary considerably. Surprisingly, this exchange rate was relatively unrelated to each Nup’s position, accessibility or role in transport, but rather correlated with its structural role; scaffold-forming Nups exchange slowly, while flexible connector Nups threading throughout the NPC’s architecture exchange more rapidly. Moreover, the cell has the capacity to destroy and replace a damaged Nup, regardless of apparent inaccessibility. Our approach provides a new window into macromolecular assembly dynamics.