Sandbox 125

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Karyopherin Beta 2 (Kapβ2) is an importin that transports various cargo proteins into the nucleus through interactions with nucleoporins, which are proteins of the nuclear pore complex (NPC). One might overlook the significance of this protein but it actually plays a crucial role in the human body by mediating transport of RNA-binding proteins involved in Transcription and RNA Processing, RNA transport and translation. The structure of Kapβ2 is composed of 20 antiparallel helices called HEAT repeats. These HEAT repeats contribute to Kapβ2’s large superhelical shape. The protein is shown to form two arches: one at the N-terminal and the other at the C-terminal. Through recognition of a nuclear localization signal (NLS) located on its cargo, Kapβ2 binds to its cargo via its C-terminal arch. Release of the cargo is mediated by RanGTP, which once bound, leads to a large movement of the 62-residue heat repeat 8 loop into the C-terminal arch. This conformational change results in the dissociation of the cargo as the b2 loop binds the NLS binding site.

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KapB2 with Ran (PDB entry 1qbk)

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