Flexible phenylalanine-glycine nucleoporins as entropic barriers to nucleocytoplasmic transport

R. Y. H. Lim, N. P. Huang, J. Koser, J. Deng, K. H. A. Lau, K. Schwarz-Herion, B. Fahrenkrog, U. Aebi

Research output: Contribution to journalArticle

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Abstract

Natively unfolded phenylalanine-glycine (FG)-repeat domains are alleged to form the physical constituents of the selective barrier-gate in nuclear pore complexes during nucleocytoplasmic transport. Presently, the biophysical mechanism behind the selective gate remains speculative because of a lack of information regarding the nanomechanical properties of the FG domains. In this work, we have applied the atomic force microscope to measure the mechanical response of individual and clusters of FG molecules. Single-molecule force spectroscopy reveals that FG molecules are unfolded and highly flexible. To provide insight into the selective gating mechanism, an experimental platform has been constructed to study the collective behavior of surface-tethered FG molecules at the nanoscale. Measurements indicate that the collective behavior of such FG molecules gives rise to an exponentially decaying long-range steric repulsive force. This finding indicates that the molecules are thermally mobile in an extended polymer brush-like conformation. This assertion is confirmed by observing that the brush-like conformation undergoes a reversible collapse transition in less polar solvent conditions. These findings reveal how FG-repeat domains may simultaneously function as an entropic barrier and a selective trap in the near-field interaction zone of nuclear pore complexes; i.e., selective gate.
LanguageEnglish
Pages9512-9517
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume103
Issue number25
DOIs
Publication statusPublished - 20 Jun 2006

Fingerprint

Nuclear Pore Complex Proteins
Phenylalanine
Glycine
Molecules
Brushes
Conformations
Polymers
Microscopes
Spectroscopy

Keywords

  • resistance
  • force spectroscopy
  • nanomechanics
  • natively unfolded proteins
  • nuclear pore complex
  • selective gating
  • atomic-force microscope
  • importin-beta binding-dynamics
  • polymer brushes
  • repeat regions
  • protein
  • adsorption
  • permeability

Cite this

Lim, R. Y. H. ; Huang, N. P. ; Koser, J. ; Deng, J. ; Lau, K. H. A. ; Schwarz-Herion, K. ; Fahrenkrog, B. ; Aebi, U. / Flexible phenylalanine-glycine nucleoporins as entropic barriers to nucleocytoplasmic transport. In: Proceedings of the National Academy of Sciences . 2006 ; Vol. 103, No. 25. pp. 9512-9517.
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abstract = "Natively unfolded phenylalanine-glycine (FG)-repeat domains are alleged to form the physical constituents of the selective barrier-gate in nuclear pore complexes during nucleocytoplasmic transport. Presently, the biophysical mechanism behind the selective gate remains speculative because of a lack of information regarding the nanomechanical properties of the FG domains. In this work, we have applied the atomic force microscope to measure the mechanical response of individual and clusters of FG molecules. Single-molecule force spectroscopy reveals that FG molecules are unfolded and highly flexible. To provide insight into the selective gating mechanism, an experimental platform has been constructed to study the collective behavior of surface-tethered FG molecules at the nanoscale. Measurements indicate that the collective behavior of such FG molecules gives rise to an exponentially decaying long-range steric repulsive force. This finding indicates that the molecules are thermally mobile in an extended polymer brush-like conformation. This assertion is confirmed by observing that the brush-like conformation undergoes a reversible collapse transition in less polar solvent conditions. These findings reveal how FG-repeat domains may simultaneously function as an entropic barrier and a selective trap in the near-field interaction zone of nuclear pore complexes; i.e., selective gate.",
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Flexible phenylalanine-glycine nucleoporins as entropic barriers to nucleocytoplasmic transport. / Lim, R. Y. H.; Huang, N. P.; Koser, J.; Deng, J.; Lau, K. H. A.; Schwarz-Herion, K.; Fahrenkrog, B.; Aebi, U.

In: Proceedings of the National Academy of Sciences , Vol. 103, No. 25, 20.06.2006, p. 9512-9517.

Research output: Contribution to journalArticle

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AU - Lim, R. Y. H.

AU - Huang, N. P.

AU - Koser, J.

AU - Deng, J.

AU - Lau, K. H. A.

AU - Schwarz-Herion, K.

AU - Fahrenkrog, B.

AU - Aebi, U.

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N2 - Natively unfolded phenylalanine-glycine (FG)-repeat domains are alleged to form the physical constituents of the selective barrier-gate in nuclear pore complexes during nucleocytoplasmic transport. Presently, the biophysical mechanism behind the selective gate remains speculative because of a lack of information regarding the nanomechanical properties of the FG domains. In this work, we have applied the atomic force microscope to measure the mechanical response of individual and clusters of FG molecules. Single-molecule force spectroscopy reveals that FG molecules are unfolded and highly flexible. To provide insight into the selective gating mechanism, an experimental platform has been constructed to study the collective behavior of surface-tethered FG molecules at the nanoscale. Measurements indicate that the collective behavior of such FG molecules gives rise to an exponentially decaying long-range steric repulsive force. This finding indicates that the molecules are thermally mobile in an extended polymer brush-like conformation. This assertion is confirmed by observing that the brush-like conformation undergoes a reversible collapse transition in less polar solvent conditions. These findings reveal how FG-repeat domains may simultaneously function as an entropic barrier and a selective trap in the near-field interaction zone of nuclear pore complexes; i.e., selective gate.

AB - Natively unfolded phenylalanine-glycine (FG)-repeat domains are alleged to form the physical constituents of the selective barrier-gate in nuclear pore complexes during nucleocytoplasmic transport. Presently, the biophysical mechanism behind the selective gate remains speculative because of a lack of information regarding the nanomechanical properties of the FG domains. In this work, we have applied the atomic force microscope to measure the mechanical response of individual and clusters of FG molecules. Single-molecule force spectroscopy reveals that FG molecules are unfolded and highly flexible. To provide insight into the selective gating mechanism, an experimental platform has been constructed to study the collective behavior of surface-tethered FG molecules at the nanoscale. Measurements indicate that the collective behavior of such FG molecules gives rise to an exponentially decaying long-range steric repulsive force. This finding indicates that the molecules are thermally mobile in an extended polymer brush-like conformation. This assertion is confirmed by observing that the brush-like conformation undergoes a reversible collapse transition in less polar solvent conditions. These findings reveal how FG-repeat domains may simultaneously function as an entropic barrier and a selective trap in the near-field interaction zone of nuclear pore complexes; i.e., selective gate.

KW - resistance

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KW - importin-beta binding-dynamics

KW - polymer brushes

KW - repeat regions

KW - protein

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