Sandbox 125: Difference between revisions
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Kapβ2 is a superhelix comprised of 20 HEAT repeats (the name HEAT derives from Huntington, Elongation factor 3 A subunit of protein phosphatase 2A and Tor1 kinase), each of which consists of two anti-parallel helices. The electrostatic potential of the internal surface of Kapβ2 superhelix at the C-terminal arch is negative. HEAT repeats 9-13 and 14-18 form the binding site of Kapβ2 cargos while repeats 1-8 constitute the Ran GTPase binding site.3 Ran GTPase, a small 216-residue protein, is found more frequently in the nucleus and enables cargos to be released from Kapβ2. | Kapβ2 is a superhelix comprised of 20 HEAT repeats (the name HEAT derives from Huntington, Elongation factor 3 A subunit of protein phosphatase 2A and Tor1 kinase), each of which consists of two anti-parallel helices. The electrostatic potential of the internal surface of Kapβ2 superhelix at the C-terminal arch is negative. HEAT repeats 9-13 and 14-18 form the binding site of Kapβ2 cargos while repeats 1-8 constitute the Ran GTPase binding site.3 Ran GTPase, a small 216-residue protein, is found more frequently in the nucleus and enables cargos to be released from Kapβ2. | ||
<font size=3> '''Kapβ2 Binding and Conformational Change''' </font> | |||
The NLSs located on KapB2 cargos are named the PY-NLS and they bind to the C-terminal arch of KapB2. | |||
Recognition of the PY-NLS by Kapβ2 follows certain guidelines: | |||
(i) PY-NLS, when not bound to Kapβ2, lacks a secondary structure. | |||
(ii) PY-NLS has an overall positive charge allowing for electrostatic compatibility with Kapβ2. | |||
(iii) General sequence for the PY-NLS is either a hydrophobic basic motif or a R-X2-5-P-Y motif at the C-terminus. | |||
The PY-NLS of 2H4M contains a hydrophobic rather than a basic N-terminal motif. Hydrophobic interactions at the N-terminal motif of the PY-NLS include: Phe273, Gly274, Pro275 and Met276 of the NLS with Trp730 and Ile773 of Kapβ2. Interactions of the C-terminal R-X2-5-P-Y motif of the NLS include: Arg284 of the NLS with Glu509 and Asp543 of Kapβ2; Pro288 and Tyr289 of the NLS with Ala380, Ala381, Asp384, Leu419, Ile457, Trp460 and Arg464 of Kapβ2. | |||
Upon binding Kapβ2,the NLS gains structure, conforms to and makes contact with the internal surface of the KapB2 C-terminal arch. | |||
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