Department for Molecular Structural Biology

Nucleo cytoplasmic trafficking

c. Import of linker Histones

Biochemical studies on the Importin-ß/Importin-7 complex and import of Histones

The nuclear import of H1 linker histones is mediated by a heterodimer of Importin-ß and Importin-7 (Fig. 1). Interestingly, both importins may interact independently with H1, but only as a dimer facilitate the translocation into the nucleus. The H1 binding site of Importin-7 comprises two extended acidic loops near the C terminus of Importin-7. Experiments using 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.

The Importin-ß interacting region of Importin 7 plays a crucial role in the activation of Importin 7 by Importin-ß. This process is allosterically regulated by Importin-ß and accounts for a specific tuning of the activity of the Importin-ß/Importin-7 heterodimer. The results provided new insights into cellular strategies to even energy balances in nuclear import and point toward a general regulation of Importin-ß-related nuclear import processes.



Linker Histones
Fig. 1. Model of an Importin-ß and Importin-7 heterodimer.
The models of the two receptors, colored in rainbow from N- to C-terminus, are shown. The blue ellipsoid highlights the postulated binding site of the histone within a central cavity formed by the two receptors.



References

  • Wohlwend, D., Strasser, A., Dickmanns, A., Doenecke, D. and Ficner R. (2007). Thermodynamic analysis of H1 nuclear import: receptor tuning of importinbeta/importin7. J. Biol. Chem. 282, 10707-10719. [Abstract]

  • Further reading
  • The requirement of H1 histones for a heterodimeric nuclear import receptor. Bäuerle M, Doenecke D, Albig W. J Biol Chem. 2002 Sep 6;277(36):32480-9. [Abstract]
  • The importin beta/importin 7 heterodimer is a functional nuclear import receptor for histone H1. Jäkel S, Albig W, Kutay U, Bischoff FR, Schwamborn K, Doenecke D, Görlich D. EMBO J. 1999 May 4;18(9):2411-23. [Abstract]