Thermodynamic analysis of H1 nuclear import: receptor tuning of importinbeta/importin7

J Biol Chem. 2007 Apr 6;282(14):10707-19. doi: 10.1074/jbc.M610409200. Epub 2007 Jan 26.

Abstract

The nuclear import of H1 linker histones is mediated by a heterodimer of transport receptors, known as importinbeta and importin7. Interestingly, both importins separately interact with H1, but only as a dimer they facilitate the translocation through the nuclear pore. We identified the H1 binding site of importin7, comprising two extended acidic loops near the C terminus of importin7. The analysis of the H1 import complex assembly by means of isothermal titration calorimetry revealed that the formation of a receptor heterodimer in vitro is an enthalpy-driven process, whereas subsequent binding of H1 to the heterodimer is entropy-driven. Furthermore, we show that the importinbeta binding domain of importin7 plays a key role in the activation of importin7 by importinbeta. This process is allosterically regulated by importinbeta and accounts for a specific tuning of the activity of the importinbeta.importin7 heterodimer. The results presented here provide new insights into cellular strategies to even energy balances in nuclear import and point toward a general regulation of importinbeta-related nuclear import processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Binding Sites
  • Cell Nucleus / metabolism*
  • Chickens
  • Dimerization
  • Entropy
  • Histones / metabolism*
  • Humans
  • Karyopherins / metabolism*
  • Models, Biological*
  • Protein Binding
  • Protein Structure, Secondary
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Xenopus laevis
  • beta Karyopherins / metabolism*

Substances

  • Histones
  • IPO7 protein, human
  • Karyopherins
  • Receptors, Cytoplasmic and Nuclear
  • beta Karyopherins