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| | ==Mouse prion protein (121-231) containing the substitution Y169G== | | ==Mouse prion protein (121-231) containing the substitution Y169G== |
| - | <StructureSection load='2l1d' size='340' side='right'caption='[[2l1d]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2l1d' size='340' side='right'caption='[[2l1d]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2l1d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L1D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L1D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2l1d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L1D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L1D FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2l1e|2l1e]], [[2l1h|2l1h]], [[2l1k|2l1k]]</div></td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2l1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l1d OCA], [https://pdbe.org/2l1d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l1d RCSB], [https://www.ebi.ac.uk/pdbsum/2l1d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l1d ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Prnp, RP23-401J24.1-001 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2l1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l1d OCA], [https://pdbe.org/2l1d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l1d RCSB], [https://www.ebi.ac.uk/pdbsum/2l1d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l1d ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/PRIO_MOUSE PRIO_MOUSE] Note=Found in high quantity in the brain of humans and animals infected with degenerative neurological diseases such as kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), etc. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PRIO_MOUSE PRIO_MOUSE] May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (By similarity). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains.<ref>PMID:12732622</ref> <ref>PMID:16492732</ref> <ref>PMID:19242475</ref> <ref>PMID:19568430</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Christen, B]] | + | [[Category: Christen B]] |
| - | [[Category: Damberger, F F]] | + | [[Category: Damberger FF]] |
| - | [[Category: Hornemann, S]] | + | [[Category: Hornemann S]] |
| - | [[Category: Perez, D R]] | + | [[Category: Perez DR]] |
| - | [[Category: Wuthrich, K]] | + | [[Category: Wuthrich K]] |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Mutation]]
| + | |
| - | [[Category: Prion]]
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| Structural highlights
Disease
PRIO_MOUSE Note=Found in high quantity in the brain of humans and animals infected with degenerative neurological diseases such as kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), etc.
Function
PRIO_MOUSE May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (By similarity). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains.[1] [2] [3] [4]
Publication Abstract from PubMed
In the otherwise highly conserved NMR structures of cellular prion proteins (PrP(C)) from different mammals, species variations in a surface epitope that includes a loop linking a beta-strand, beta2, with a helix, alpha2, are associated with NMR manifestations of a dynamic equilibrium between locally different conformations. Here, it is shown that this local dynamic conformational polymorphism in mouse PrP(C) is eliminated through exchange of Tyr169 by Ala or Gly, but is preserved after exchange of Tyr 169 with Phe. NMR structure determinations of designed variants of mouse PrP(121-231) at 20 degrees C and of wild-type mPrP(121-231) at 37 degrees C together with analysis of exchange effects on NMR signals then resulted in the identification of the two limiting structures involved in this local conformational exchange in wild-type mouse PrP(C), and showed that the two exchanging structures present characteristically different solvent-exposed epitopes near the beta2-alpha2 loop. The structural data presented in this paper provided a platform for currently ongoing, rationally designed experiments with transgenic laboratory animals for renewed attempts to unravel the so far elusive physiological function of the cellular prion protein.
Cellular prion protein conformation and function.,Damberger FF, Christen B, Perez DR, Hornemann S, Wuthrich K Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17308-13. Epub 2011 Oct 10. PMID:21987789[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mani K, Cheng F, Havsmark B, Jonsson M, Belting M, Fransson LA. Prion, amyloid beta-derived Cu(II) ions, or free Zn(II) ions support S-nitroso-dependent autocleavage of glypican-1 heparan sulfate. J Biol Chem. 2003 Oct 3;278(40):38956-65. Epub 2003 May 5. PMID:12732622 doi:10.1074/jbc.M300394200
- ↑ Steele AD, Emsley JG, Ozdinler PH, Lindquist S, Macklis JD. Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis. Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3416-21. Epub 2006 Feb 21. PMID:16492732 doi:10.1073/pnas.0511290103
- ↑ Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature. 2009 Feb 26;457(7233):1128-32. doi: 10.1038/nature07761. PMID:19242475 doi:10.1038/nature07761
- ↑ Singh A, Kong Q, Luo X, Petersen RB, Meyerson H, Singh N. Prion protein (PrP) knock-out mice show altered iron metabolism: a functional role for PrP in iron uptake and transport. PLoS One. 2009 Jul 1;4(7):e6115. doi: 10.1371/journal.pone.0006115. PMID:19568430 doi:10.1371/journal.pone.0006115
- ↑ Damberger FF, Christen B, Perez DR, Hornemann S, Wuthrich K. Cellular prion protein conformation and function. Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17308-13. Epub 2011 Oct 10. PMID:21987789 doi:10.1073/pnas.1106325108
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