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Karyopherin-centric control of nuclear pores based on molecular occupancy and kinetic analysis of multivalent binding with FG nucleoporins.
Kapinos LE
,
Schoch RL
,
Wagner RS
,
Schleicher KD
,
Lim RY
.
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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.
Alber,
The molecular architecture of the nuclear pore complex.
2007, Pubmed
Alber,
The molecular architecture of the nuclear pore complex.
2007,
Pubmed
Ando,
Physical motif clustering within intrinsically disordered nucleoporin sequences reveals universal functional features.
2013,
Pubmed
Atkinson,
Conserved spatial organization of FG domains in the nuclear pore complex.
2013,
Pubmed
Bayliss,
Structural basis for the interaction between NTF2 and nucleoporin FxFG repeats.
2002,
Pubmed
Bayliss,
GLFG and FxFG nucleoporins bind to overlapping sites on importin-beta.
2002,
Pubmed
Bayliss,
Structural basis for the interaction between FxFG nucleoporin repeats and importin-beta in nuclear trafficking.
2000,
Pubmed
Bayliss,
Interaction between NTF2 and xFxFG-containing nucleoporins is required to mediate nuclear import of RanGDP.
1999,
Pubmed
,
Xenbase
Beck,
Nuclear pore complex structure and dynamics revealed by cryoelectron tomography.
2004,
Pubmed
Bednenko,
Importin beta contains a COOH-terminal nucleoporin binding region important for nuclear transport.
2003,
Pubmed
Ben-Efraim,
Gradient of increasing affinity of importin beta for nucleoporins along the pathway of nuclear import.
2001,
Pubmed
Bright,
Predicting properties of intrinsically unstructured proteins.
2001,
Pubmed
Chatel,
Domain topology of nucleoporin Nup98 within the nuclear pore complex.
2012,
Pubmed
,
Xenbase
Chook,
Nuclear import by karyopherin-βs: recognition and inhibition.
2011,
Pubmed
Colwell,
Charge as a selection criterion for translocation through the nuclear pore complex.
2010,
Pubmed
Cronshaw,
Proteomic analysis of the mammalian nuclear pore complex.
2002,
Pubmed
Dange,
Autonomy and robustness of translocation through the nuclear pore complex: a single-molecule study.
2008,
Pubmed
Denning,
Disorder in the nuclear pore complex: the FG repeat regions of nucleoporins are natively unfolded.
2003,
Pubmed
Devos,
Simple fold composition and modular architecture of the nuclear pore complex.
2006,
Pubmed
Fahrenkrog,
Domain-specific antibodies reveal multiple-site topology of Nup153 within the nuclear pore complex.
2002,
Pubmed
,
Xenbase
Fasting,
Multivalency as a chemical organization and action principle.
2012,
Pubmed
Frenkiel-Krispin,
Structural analysis of a metazoan nuclear pore complex reveals a fused concentric ring architecture.
2010,
Pubmed
,
Xenbase
Frey,
A saturated FG-repeat hydrogel can reproduce the permeability properties of nuclear pore complexes.
2007,
Pubmed
Frey,
FG/FxFG as well as GLFG repeats form a selective permeability barrier with self-healing properties.
2009,
Pubmed
Gjelstrup,
The role of nanometer-scaled ligand patterns in polyvalent binding by large mannan-binding lectin oligomers.
2012,
Pubmed
Grossman,
Functional architecture of the nuclear pore complex.
2012,
Pubmed
Görlich,
Distinct functions for the two importin subunits in nuclear protein import.
1995,
Pubmed
,
Xenbase
Hülsmann,
The permeability of reconstituted nuclear pores provides direct evidence for the selective phase model.
2012,
Pubmed
,
Xenbase
Isgro,
Binding dynamics of isolated nucleoporin repeat regions to importin-beta.
2005,
Pubmed
Jovanovic-Talisman,
Artificial nanopores that mimic the transport selectivity of the nuclear pore complex.
2009,
Pubmed
Kapinos,
Karyopherin-Centric Control of Nuclear Pores Based on Molecular Occupancy and Kinetic Analysis of Multivalent Binding with FG Nucleoporins.
2018,
Pubmed
Keminer,
Permeability of single nuclear pores.
1999,
Pubmed
,
Xenbase
Kowalczyk,
Single-molecule transport across an individual biomimetic nuclear pore complex.
2011,
Pubmed
Labokha,
Systematic analysis of barrier-forming FG hydrogels from Xenopus nuclear pore complexes.
2013,
Pubmed
,
Xenbase
Lim,
Flexible phenylalanine-glycine nucleoporins as entropic barriers to nucleocytoplasmic transport.
2006,
Pubmed
Lim,
Nanomechanical basis of selective gating by the nuclear pore complex.
2007,
Pubmed
,
Xenbase
Lott,
The importin beta binding domain modulates the avidity of importin beta for the nuclear pore complex.
2010,
Pubmed
Ma,
Self-regulated viscous channel in the nuclear pore complex.
2012,
Pubmed
Ma,
Three-dimensional distribution of transient interactions in the nuclear pore complex obtained from single-molecule snapshots.
2010,
Pubmed
Mammen,
Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors.
1998,
Pubmed
Milles,
Facilitated aggregation of FG nucleoporins under molecular crowding conditions.
2013,
Pubmed
Munoz,
Real-time evaluation of binding mechanisms in multivalent interactions: a surface plasmon resonance kinetic approach.
2013,
Pubmed
Opferman,
Morphology of polymer brushes infiltrated by attractive nanoinclusions of various sizes.
2013,
Pubmed
Paine,
Nuclear envelope permeability.
1975,
Pubmed
Paradise,
Significant proportions of nuclear transport proteins with reduced intracellular mobilities resolved by fluorescence correlation spectroscopy.
2007,
Pubmed
Patel,
Natively unfolded nucleoporins gate protein diffusion across the nuclear pore complex.
2007,
Pubmed
Paulillo,
Nucleoporin domain topology is linked to the transport status of the nuclear pore complex.
2005,
Pubmed
,
Xenbase
Peleg,
Converging on the function of intrinsically disordered nucleoporins in the nuclear pore complex.
2010,
Pubmed
Peters,
Translocation through the nuclear pore complex: selectivity and speed by reduction-of-dimensionality.
2005,
Pubmed
Peters,
Translocation through the nuclear pore: Kaps pave the way.
2009,
Pubmed
Rout,
Virtual gating and nuclear transport: the hole picture.
2003,
Pubmed
Rout,
The yeast nuclear pore complex: composition, architecture, and transport mechanism.
2000,
Pubmed
Schoch,
Nuclear transport receptor binding avidity triggers a self-healing collapse transition in FG-nucleoporin molecular brushes.
2012,
Pubmed
Schoch,
Non-interacting molecules as innate structural probes in surface plasmon resonance.
2013,
Pubmed
Schwarz-Herion,
Domain topology of the p62 complex within the 3-D architecture of the nuclear pore complex.
2007,
Pubmed
,
Xenbase
Solmaz,
Molecular architecture of the transport channel of the nuclear pore complex.
2011,
Pubmed
Stewart,
Molecular mechanism of the nuclear protein import cycle.
2007,
Pubmed
Strawn,
Minimal nuclear pore complexes define FG repeat domains essential for transport.
2004,
Pubmed
Svitel,
Combined affinity and rate constant distributions of ligand populations from experimental surface binding kinetics and equilibria.
2003,
Pubmed
Svitel,
Probing the functional heterogeneity of surface binding sites by analysis of experimental binding traces and the effect of mass transport limitation.
2007,
Pubmed
Tagliazucchi,
Effect of charge, hydrophobicity, and sequence of nucleoporins on the translocation of model particles through the nuclear pore complex.
2013,
Pubmed
Terry,
Flexible gates: dynamic topologies and functions for FG nucleoporins in nucleocytoplasmic transport.
2009,
Pubmed
Tetenbaum-Novatt,
Nucleocytoplasmic transport: a role for nonspecific competition in karyopherin-nucleoporin interactions.
2012,
Pubmed
Tokunaga,
Highly inclined thin illumination enables clear single-molecule imaging in cells.
2008,
Pubmed
Xu,
In vivo analysis of human nucleoporin repeat domain interactions.
2013,
Pubmed
Yamada,
A bimodal distribution of two distinct categories of intrinsically disordered structures with separate functions in FG nucleoporins.
2010,
Pubmed
Yang,
Nuclear import time and transport efficiency depend on importin beta concentration.
2006,
Pubmed
Zilman,
Efficiency, selectivity, and robustness of nucleocytoplasmic transport.
2007,
Pubmed