Thermodynamic analysis of H1 nuclear import: receptor tuning of importinbeta/importin7.
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.
Wohlwend
Daniel
D
Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik and GZMB, Georg-August-Universität Göttingen, D-37077 Göttingen, Germany.
Strasser
Anja
A
Dickmanns
Achim
A
Doenecke
Detlef
D
Ficner
Ralf
R
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism*; D002645:Chickens; D019281:Dimerization; D019277:Entropy; D006657:Histones / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D017433:Protein Structure, Secondary; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014982:Xenopus laevis; D028961:beta Karyopherins / Q000378:metabolism*
D006657:Histones; C466996:IPO7 protein, human; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D028961:beta Karyopherins