Sandbox 148

Karyopharin Beta 2

Karyopherinβ is a group of proteins that is composed of both importins and exportins. Importins are proteins that carry cargos into the nucleus while exportins serve the opposite function. As of today, twenty different Kapβs have been identified. Each of these Kapβs is capable of recognizing and transporting a specific group of cargos. In order to bind to its cargo a Kapβ has to recognize a Nuclear Localization or Export Signal (NLS or NES).

Karyopherin beta 2 (kapβ2) is an importin that transports various cargo protein into the nucleus through interactions with nucleoporins, which are proteins of the nucleopore complex (NPC). One might overlook the significance of this protein but actually plays a crucial role in the human body by mediating transport of RNA- binding proteins involved in transcription, RNA processing, RNA transport and translation. The structure of KAPβ is composed of 20 antiparallel helices called HEAT repeats. These repeats contribute to kapβ2’s large . That form two arches: one at the and the other at the . 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, modifies the shape of kapβ2. Release of the cargo is mediated once contact occurs between RanGTP and N-terminal arch of Kapβ2.

How does Kapβ2 identify its cargo?

The NLS located on Kapβ2 cargos, are named the PY-NLS and they bind to the C-terminal arch of Kapβ2. The internal surface of kapβ2 superhelix at the C-terminal arch has negative electrostatic potential. The recognition of the by Kapβ2 follows certain guidelines: (1) PY-NLS, when not bound to Kapβ2, lacks a secondary structure; (2) PY-NLS has an overall positive charge allowing for electrostatic compatibility with Kapβ2; (3) the general sequence for PY-NLS is either a hydrophobic or a basic motif at the N-terminus and a R-X_2-5P-Y motif at the C-terminus.

The PY-NLS of 4OO6 contains a basic rather than a hydrophobic N-terminal motif. Basic interactions at the N-terminal motif pf the PY-NLS include: Arg 92, Arg 94 and Arg 96 of the NLS with Glu 588 and Glu 496 of Kapβ2. Interactions of the C-terminal R-X_2-5P-Y motif of the NLS include: Pro 98 of the NLS with Ile 456 and Trp 459 of Kapβ2.