Npc

▲ FIGURE 12-21 Mechanism for nuclear import of "cargo" proteins. In the cytoplasm (bottom), a free importin binds to the NLS of a cargo protein, forming a bimolecular cargo complex. In the case of a basic NLS, the adapter protein importin a bridges the NLS and importin p, forming a trimolecular cargo complex (not shown). The cargo complex diffuses through the NPC by interacting with successive FG-nucleoporins. In the nucleoplasm, interaction of Ran-GTP with the importin causes a conformational change that decreases its affinity for the NLS, releasing the cargo. To support another cycle of import, the importin-Ran-GTP complex is transported back to the cytoplasm. A GTPase-accelerating protein (GAP) associated with the cytoplasmic filaments of the NPC stimulates Ran to hydrolyze the bound GTP This generates a conformational change causing dissociation from the importin, which can then initiate another round of import. Ran-GDP is bound by NTF2 (not shown) and returned to the nucleoplasm, where a guanine nucleotide-exchange factor (GEF) causes release of GDP and rebinding of GTP

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