Thermodynamic characterization of the multivalent interactions underlying rapid and selective translocation through the nuclear pore complex

Ryo Hayama, Samuel Sparks, Lee M. Hecht, Kaushik Dutta, Jerome M. Karp, Christina M. Cabana, Michael P. Rout, David Cowburn, Norma M. Allewell

Research output: Contribution to journalReview article

8 Citations (Scopus)

Abstract

Intrinsically disordered proteins (IDPs) play important roles in many biological systems. Given the vast conformational space that IDPs can explore, the thermodynamics of the interactions with their partners isclosely linked to their biological functions. Intrinsically disordered regions of Phe-Gly nucleoporins (FG Nups) that contain multiple phenylalanine-glycine repeats are of particular interest, astheir interactions with transport factors (TFs) underlie the paradoxically rapid yet also highly selective transportofmacromolecules mediatedbythe nuclear pore complex. Here, we used NMR and isothermal titration calorimetry to thermodynamically characterize these multivalent interactions. These analyses revealed that a combination of low per-FG motif affinity and the enthalpy-entropy balance prevents high-avidity interaction between FG Nups and TFs, whereas the large number of FG motifs promotes frequent FG-TF contacts, resulting in enhanced selectivity. Our thermodynamic model underlines the importance of functional disorder of FG Nups. It helps explain the rapid and selective translocation of TFs through the nuclear pore complex and further expands our understanding of the mechanisms of "fuzzy" interactions involving IDPs.

Original languageEnglish (US)
Pages (from-to)4555-4563
Number of pages9
JournalJournal of Biological Chemistry
Volume293
Issue number12
DOIs
StatePublished - Jan 1 2018

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Intrinsically Disordered Proteins
Nuclear Pore
Thermodynamics
phenylalanylglycine
Nuclear Pore Complex Proteins
Calorimetry
Entropy
Biological systems
Phenylalanine
Titration
Glycine
Enthalpy
Nuclear magnetic resonance

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Thermodynamic characterization of the multivalent interactions underlying rapid and selective translocation through the nuclear pore complex. / Hayama, Ryo; Sparks, Samuel; Hecht, Lee M.; Dutta, Kaushik; Karp, Jerome M.; Cabana, Christina M.; Rout, Michael P.; Cowburn, David; Allewell, Norma M.

In: Journal of Biological Chemistry, Vol. 293, No. 12, 01.01.2018, p. 4555-4563.

Research output: Contribution to journalReview article

Hayama, Ryo ; Sparks, Samuel ; Hecht, Lee M. ; Dutta, Kaushik ; Karp, Jerome M. ; Cabana, Christina M. ; Rout, Michael P. ; Cowburn, David ; Allewell, Norma M. / Thermodynamic characterization of the multivalent interactions underlying rapid and selective translocation through the nuclear pore complex. In: Journal of Biological Chemistry. 2018 ; Vol. 293, No. 12. pp. 4555-4563.
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AU - Cabana, Christina M.

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