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.




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