期刊
BIOPHYSICAL JOURNAL
卷 108, 期 4, 页码 918-927出版社
CELL PRESS
DOI: 10.1016/j.bpj.2014.12.041
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资金
- Swiss National Science Foundation
- Biozentrum
- Swiss Nanoscience Institute
- Medical Research Council [U105178939]
- Wellcome Trust [080522]
- MRC [MC_U105178939] Funding Source: UKRI
- Medical Research Council [MC_U105178939] Funding Source: researchfish
The transport channel of nuclear pore complexes (NPCs) contains a high density of intrinsically disordered proteins that are rich in phenylalanine-glycine (FG)-repeat motifs (FG Nups). The FG Nups interact promiscuously with various nuclear transport receptors (NTRs), such as karyopherins (Kaps), that mediate the trafficking of nucleocytoplasmic cargoes while also generating a selectively permeable barrier against other macromolecules. Although the binding of NTRs to FG Nups increases molecular crowding in the NPC transport channel, it is unclear how this impacts FG Nup barrier function or the movement of other molecules, such as the Ran importer NTF2. Here, we use surface plasmon resonance to evaluate FG Nup conformation, binding equilibria, and interaction kinetics associated with the multivalent binding of NTF2 and karyopherin beta 1 (Kap beta 1) to Nsp1p molecular brushes. NTF2 and Kap beta 1 show different long- and short-lived binding characteristics that emerge from varying degrees of molecular retention and FG repeat binding avidity within the Nsp1p brush. Physiological concentrations of NTF2 produce a collapse of Nsp1p brushes, whereas Kap beta 1 binding generates brush extension. However, the presence of prebound Kap beta 1 inhibits Nsp1p brush collapse during NTF2 binding, which is dominated by weak, short-lived interactions that derive from steric hindrance and diminished avidity with Nsp1p. This suggests that binding promiscuity confers kinetic advantages to NTF2 by expediting its facilitated diffusion and reinforces the proposal that Kap beta 1 contributes to the integral barrier function of the NPC.
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