Importin
As part of a heterodimer, importin-β mediates interactions with the pore complex, while importin-α acts as an adaptor protein to bind the nuclear localization signal (NLS) on the cargo.
The NLS-Importin α-Importin β trimer dissociates after binding to Ran GTP inside the nucleus,[2] with the two importin proteins being recycled to the cytoplasm for further use.
Importin-α was first isolated in 1994 by a group including Enno Hartmann, based at the Max Delbrück Center for Molecular Medicine.
It was cloned, sequenced and expressed in E.coli and in order to completely reconstitute signal dependent transport, had to be combined with Ran(TC4).
[5] These groups found that importin-α requires another protein, importin-β to function, and that together they form a receptor for nuclear localization signals (NLS), thus allowing transport into the nucleus.
A large proportion of the importin-α adaptor protein is made up of several armadillo repeats (ARM) arranged in tandem.
These repeats can stack together to form a curved-shaped structure, which facilitates binding to the NLS of specific cargo proteins.
Crystallographic analysis has shown that these motifs bind to importin-β at shallow hydrophobic pockets found on its surface.
[7] The release of importin-β frees this region and allows it to loop back and compete for binding with the cargo protein at the major NLS-binding site.
[11] Finally, in order to return to the cytoplasm, importin-α must associate with a Ran-GTP/CAS (nuclear export factor) complex which facilitates its exit from the nucleus.
CAS (cellular apoptosis susceptibility protein) is part of the importin-β superfamily of karyopherins and is defined as a nuclear export factor.
[13] In addition, importin-α has been shown to transport the tumour suppressor gene, BRCA1 (breast cancer type 1 susceptibility protein), into the nucleus.
Although importin-α and importin-β are used to describe importin as a whole, they actually represent larger families of proteins that share a similar structure and function.
