Nucleoporins' exclusive amino acid sequence features regulate their transient interaction with and selectivity of cargo complexes in the nuclear pore
Nucleocytoplasmic transport is a vital cellular process yet to be fully understood. Among several elements that are involved in the transport process, FG Nups are the major role players. We observed that specific sequence features (called like-charge regions, or lpLCRs), namely the extended sub-sequences that only possess positively charged amino acids, significantly affect the conformation of FG Nups inside the NPC. Here we investigate how the presence of lpLCRs affects the interactions between FG Nups and their interactions with cargo complex. We combined coarse-grained molecular dynamics simulations with time-resolved force distribution analysis to disordered proteins to explore the behavior of the system. Our results suggest that the number of charged residues in the lpLCR domain directly governs the average distance between Phe residues and the intensity of interaction between them. As a result, the number of charged residues within and lpLCR determines the balance between the hydrophobic interaction and electrostatic repulsion and governs how disordered the hydrophobic network formed by FG Nups. Moreover, changing the number of charged residues in an lpLCR domain can interfere with ultrafast and transient interactions between FG Nups and cargo complex. [Media: see text] [Media: see text] [Media: see text]