Sandbox 122

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Karyopherin Beta 2 :)

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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 called HEATrepeats. These HEAT repeats contribute to kapβ2’s large superhelical shape. 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 Recognizes Cargo In the Cytoplasm

The NLS located on Kapβ2 cargos are named PY-NLS and they bind to the C-terminal arch of Kapβ2. The electrostatic potential of the internal surface of Kapβ2 superhelix at the C-terminal arch is negative

Recognition the PY-NLS by Kapβ2 follows a certain guidelines:

  1. PY-NLS, when not bound to Kapβ2, lacks a secondary structure.
  2. PY-NLS hass an overall allowing for electrostatic compatibility with Kapβ2.
  3. General sequence for the PY-NLS is either a hydrophobic or base at the motif at N-terminus and R-X2-5- P-Y motif at the C-terminus

The PY-NLS of 4OO6 contains a basic rather than hydrophobic N-terminal motif. motif of the PY-NLS include: Arg92, Arg94, and Arg96 of the NLS with Glu588 and Glu496 of Kapβ2. R-X2-5- P-Y motif of the NLS include: Pro98 and Tyr99 of the NLS with Ala381,Ala382, Ala423, Ile457, and Trp460 of Kapβ2.

Upon binding Kapβ2, the NLS structure conforms to and makes contact with the internal surface of Kapβ2 C-terminal arch

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