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Importins
Exit Strategy
Once the importin-beta/importin-alpha/cargo complex gets inside the nucleus, the cargo must be released and the importins must be recycled back to the cytoplasm. The Ran protein, shown here in red, is responsible for releasing the cargo. It binds to importin-beta and causes a significant change in shape, leading to the release of importin-alpha and the cargo. Then, the complex of importin-beta and Ran (shown on the left, PDB entry 2bku) travels back through the pore. Outside, a GTP molecule in Ran (shown in bright red) is cleaved and the Ran dissociates, leaving importin-beta ready to carry the next cargo protein inside. Importin-alpha can't get back to the cytoplasm by itself, so it gets some help from CAS (a nuclear export factor), shown here on the right in purple (PDB entry 1wa5). CAS is similar to importin-beta, but moves through the nuclear pore in the opposite direction. It binds to importin-alpha and Ran and carries them out of the nucleus. Then, a similar cleavage of the GTP in Ran releases importin-alpha for another round of transport.
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Last changed by: A.Honegger,