Prion protein: Difference between revisions
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<StructureSection load='1hjm' size='350' side='right' scene='Prion_protein/Cartoon/4' caption=' NMR structure of human prion protein precursor globular domain (PDB code [[1hjm]])'> | |||
The [[prion protein]] (PrP) is a cell surface glycoprotein, which can exist in two alternatively folded conformations: a cellular isoform denoted (PrP<sup>C</sup>) and a disease associated isoform termed PrP<sup>Sc</sup>. | The [[prion protein]] (PrP) is a cell surface glycoprotein, which can exist in two alternatively folded conformations: a cellular isoform denoted (PrP<sup>C</sup>) and a disease associated isoform termed PrP<sup>Sc</sup>. | ||
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==Structure of PrP<sup>C</sup>== | ==Structure of PrP<sup>C</sup>== | ||
PrP<sup>C</sup> has | PrP<sup>C</sup> has an [http://proteopedia.org/w/Intrinsically_Disordered_Protein intrinsically disordered] N-terminal region, and a predominantly α-helical C-terminal region from residues ~120-230, containing three α-helices and two short <scene name='Prion_protein/Cartoon/3'>β-strands</scene>. A <scene name='Prion_protein/1hjm_disulfide_bond/4'>single disulfide bond</scene> connects the middle of helices 2 and 3. The presence of the N-terminal region has little impact on the structure of the C-terminal domain <ref>Zahn, R ''et al.'' (2000) NMR solution structure of the human prion protein ''Proc. Natl. Acad. Sci. USA'' '''97''', 145-150</ref>. The structure of PrP<sup>C</sup> is highly conserved amongst mammals, and only differs slightly in birds, reptiles and amphibians<ref>Calzolai, L ''et al.'' (2005) Prion protein NMR structures of chicken, turtle, and frog ''Proc. Natl. Acad. Sci. USA'' '''102''', 651-655</ref>. | ||
The vast majority of structures have been determined by NMR spectroscopy, but two structures have been reported by X-ray crystallography. In sheep PrP, the X-ray structure is similar to those determined by NMR spectroscopy, however in human PrP, the X-ray structure is a dimer in which helix 3 is swapped between monomers, and the disulphide bond is rearranged to be intermolecular between the dimer subunits. | The vast majority of structures have been determined by NMR spectroscopy, but two structures have been reported by X-ray crystallography. In sheep PrP, the X-ray structure is similar to those determined by NMR spectroscopy, however in human PrP, the X-ray structure is a dimer in which helix 3 is swapped between monomers, and the disulphide bond is rearranged to be intermolecular between the dimer subunits. | ||
==Models of PrP<sup>Sc</sup> structure== | ==Models of PrP<sup>Sc</sup> structure== | ||
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study revealed that slow fluctuation on a time scale of microseconds to milliseconds occurs, again, in helices 2 and 3<ref>Kuwata, K. ''et al.'' (2004) Slow conformational dynamics in the hamster prion protein ''Biochemistry'' '''43''', 4439-4446</ref>,<ref>Korzhnev, D.M. ''et al.'' (2004) Low-populated folding intermediates of Fyn SH3 characterized by relaxation dispersion NMR ''Nature'' '''430''', 586-590</ref>. | study revealed that slow fluctuation on a time scale of microseconds to milliseconds occurs, again, in helices 2 and 3<ref>Kuwata, K. ''et al.'' (2004) Slow conformational dynamics in the hamster prion protein ''Biochemistry'' '''43''', 4439-4446</ref>,<ref>Korzhnev, D.M. ''et al.'' (2004) Low-populated folding intermediates of Fyn SH3 characterized by relaxation dispersion NMR ''Nature'' '''430''', 586-590</ref>. | ||
== | == See Also == | ||
* [[Prion]] | |||
* [[Journal:JBSD:4]] | |||
* [[ | |||
* [[ | |||
==References== | ==References== | ||
<references/> | <references/> | ||
</StructureSection> | |||
[[Category:Topic Page]] | |||