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- W2009084328 abstract "Intrinsically disordered Phe-Gly nucleoporins (FG Nups) within nuclear pore complexes exert multivalent interactions with transport receptors (Karyopherins (Kaps)) that orchestrate nucleocytoplasmic transport. Current FG-centric views reason that selective Kap translocation is promoted by alterations in the barrier-like FG Nup conformations. However, the strong binding of Kaps with the FG Nups due to avidity contradicts rapid Kap translocation in vivo. Here, using surface plasmon resonance, we innovate a means to correlate in situ mechanistic (molecular occupancy and conformational changes) with equilibrium (binding affinity) and kinetic (multivalent binding kinetics) aspects of Karyopherinβ1 (Kapβ1) binding to four different FG Nups. A general feature of the FxFG domains of Nup214, Nup62, and Nup153 is their capacity to extend and accommodate large numbers of Kapβ1 molecules at physiological Kapβ1 concentrations. A notable exception is the GLFG domain of Nup98, which forms a partially penetrable cohesive layer. Interestingly, we find that a slowly exchanging Kapβ1 phase forms an integral constituent within the FG Nups that coexists with a fast phase, which dominates transport kinetics due to limited binding with the pre-occupied FG Nups at physiological Kapβ1 concentrations. Altogether, our data reveal an emergent Kap-centric barrier mechanism that may underlie mechanistic and kinetic control in the nuclear pore complex." @default.
- W2009084328 created "2016-06-24" @default.
- W2009084328 creator A5003513749 @default.
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- W2009084328 date "2014-04-01" @default.
- W2009084328 modified "2023-10-16" @default.
- W2009084328 title "Karyopherin-Centric Control of Nuclear Pores Based on Molecular Occupancy and Kinetic Analysis of Multivalent Binding with FG Nucleoporins" @default.
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- W2009084328 doi "https://doi.org/10.1016/j.bpj.2014.02.021" @default.
- W2009084328 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6302222" @default.
- W2009084328 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30527336" @default.
- W2009084328 hasPublicationYear "2014" @default.
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