Inside cells, communication between the nucleus, which harbours our precious genetic material, and the cytoplasm is mediated by the constant exchange of thousands of signalling molecules and proteins that are gated through giant nuclear pore complexes (NPC). Until now, it was unknown how this traffic can be so fast and yet precise enough to prevent the passage of unwanted molecules. Through a combination of computer simulations and various experimental techniques it was now shown that the very flexible and disordered protein that fill the NPC conduit can bind to its transport receptor within billionths of a second. The new study suggests that many binding motifs at the surface of the flexible IDP create a highly reactive surface that together with the very high speed of locking and unlocking ensures efficient proof-reading while the receptors travel so fast through the NPC. Since many pathogens have adapted strategies to use the hosts native nucleoctyplasmic transport machinery in order to deliver their genetic material into the nucleus, these results form the basis for a better understanding on pathogen invasion mechanism.
Cell. 9 October 2015. DOI: 10.1016/j.cell.2015.09.047