Protein import, nucleus GTPases

Nuclear importation is mediated by a number of proteins that cycle between the cytosol and the nucleus (Fig. 27-37), including importin a and J8 and a small GTPase known as Ran. A heterodimer of importin a and J8 functions as a soluble receptor for proteins targeted to the nucleus, with the a subunit binding NLS-bearing... 

Fig. 5. The cellular compartment defines the nucleotide state of Ran. In the cytosol a Ran-specific GTPase activating protein (RanGAP) ensures that Ran exists almost exclusively in the GDP-complexed state. In the nucleus a Ran nucleotide exchange factor (RCC1) catalyzes the exchange reaction from Ran GDP towards Ran GTP. Import and export complexes recognize their actual cellular environment by interaction with the Ran protein...

Fig. 10.22. Nuclear import. Proteins with the nuclear localization signal bind to importins, which carry them through the nuclear pore into the nucleus. The monomeric G protein Ran containing bound GTP binds to one of the subunits of importin. This causes dissociation of the importin subunits and release of the imported protein in the nucleus. The Ran-importin complex exits a nuclear pore. On the cytoplasmic side, a RanGAP (GTPase activating protein) activates the hydrolysis of GTP to GDP, which causes dissociation of the complex. RanGDP is subsequently returned to the nucleus, where an accessory protein activates dissociation of GDP and association of GTP.

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