The importin beta/importin 7 heterodimer is a functional nuclear import receptor for histone H1.
Import of proteins into the nucleus proceeds through nuclear pore complexes and is largely mediated by nuclear transport receptors of the importin beta family that use direct RanGTP-binding to regulate the interaction with their cargoes. We investigated nuclear import of the linker histone H1 and found that two receptors, importin beta (Impbeta) and importin 7 (Imp7, RanBP7), play a critical role in this process. Individually, the two import receptors bind H1 weakly, but binding is strong for the Impbeta/Imp7 heterodimer. Consistent with this, import of H1 into nuclei of permeabilized mammalian cells requires exogenous Impbeta together with Imp7. Import by the Imp7/Impbeta heterodimer is strictly Ran dependent, the Ran-requiring step most likely being the disassembly of the cargo-receptor complex following translocation into the nucleus. Disassembly is brought about by direct binding of RanGTP to Impbeta and Imp7, whereby the two Ran-binding sites act synergistically. However, whereas an Impbeta/RanGTP interaction appears essential for H1 import, Ran-binding to Imp7 is dispensable. Thus, Imp7 can function in two modes. Its Ran-binding site is essential when operating as an autonomous import receptor, i.e. independently of Impbeta. Within the Impbeta/Imp7 heterodimer, however, Imp7 plays a more passive role than Impbeta and resembles an import adapter.
Jäkel
S
S
Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
Albig
W
W
Kutay
U
U
Bischoff
F R
FR
Schwamborn
K
K
Doenecke
D
D
Görlich
D
D
D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D019281:Dimerization; D006160:Guanosine Triphosphate / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D028884:Karyopherins; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014981:Xenopus; D020931:ran GTP-Binding Protein
D006657:Histones; D028884:Karyopherins; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D006160:Guanosine Triphosphate; D020931:ran GTP-Binding Protein