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| | ==Syrian hamster prion protein with thiamine== | | ==Syrian hamster prion protein with thiamine== |
| - | <StructureSection load='2lh8' size='340' side='right' caption='[[2lh8]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='2lh8' size='340' side='right'caption='[[2lh8]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2lh8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Golden_hamster Golden hamster]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LH8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LH8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2lh8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Golden_hamster Golden hamster]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LH8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LH8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=VIB:3-(4-AMINO-2-METHYL-PYRIMIDIN-5-YLMETHYL)-5-(2-HYDROXY-ETHYL)-4-METHYL-THIAZOL-3-IUM'>VIB</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VIB:3-(4-AMINO-2-METHYL-PYRIMIDIN-5-YLMETHYL)-5-(2-HYDROXY-ETHYL)-4-METHYL-THIAZOL-3-IUM'>VIB</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRNP, PRP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10036 Golden hamster])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRNP, PRP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10036 Golden hamster])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lh8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lh8 OCA], [http://pdbe.org/2lh8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lh8 RCSB], [http://www.ebi.ac.uk/pdbsum/2lh8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2lh8 ProSAT]</span></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=2lh8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lh8 OCA], [https://pdbe.org/2lh8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lh8 RCSB], [https://www.ebi.ac.uk/pdbsum/2lh8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lh8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PRIO_MESAU PRIO_MESAU]] 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. | + | [[https://www.uniprot.org/uniprot/PRIO_MESAU PRIO_MESAU]] 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 == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PRIO_MESAU PRIO_MESAU]] 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). 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 (By similarity).<ref>PMID:19059915</ref> | + | [[https://www.uniprot.org/uniprot/PRIO_MESAU PRIO_MESAU]] 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). 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 (By similarity).<ref>PMID:19059915</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Prion|Prion]] | + | *[[Prion 3D structures|Prion 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Golden hamster]] | | [[Category: Golden hamster]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Abera, A]] | | [[Category: Abera, A]] |
| | [[Category: Berjanskii, M]] | | [[Category: Berjanskii, M]] |
| Structural highlights
Disease
[PRIO_MESAU] 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_MESAU] 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). 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 (By similarity).[1]
Publication Abstract from PubMed
Summary: While highly conserved throughout evolution, the exact biological function of the prion protein is still unclear. In an effort to identify the potential biological functions of the prion protein we conducted a small-molecule screening assay with the Syrian hamster prion protein (shPrP 90-232). The screen was performed using a library of 149 water-soluble metabolites that are known to pass through the blood-brain barrier. Using a combination of 1D-NMR, fluorescence quenching and surface plasmon resonance we identified thiamine (vitamin B1) as a specific prion ligand with a binding constant of approximately 60 muM. Subsequent studies showed that this interaction is evolutionarily conserved, with similar binding constants being seen for mouse, hamster and human prions. Various protein construct lengths, both with and without the unstructured N-terminal region in the presence and absence of copper, were examined. This indicates the N-terminus has no influence on the protein's ability to interact with thiamine. In addition to thiamine, the more biologically abundant forms of vitamin B1 (thiamine monophosphate and thiamine diphosphate) were also found to bind the prion protein with similar affinity. Heteronuclear NMR experiments were used to determine thiamine's interaction site, which is located between helix 1 and the preceding loop. These data in conjunction with computer-aided docking and molecular dynamics were used to model the thiamine-binding pharmacophore and a comparison with other thiamine binding proteins was performed to reveal the common features of interaction.
The Prion Protein Binds Thiamine.,Perez-Pineiro R, Bjorndahl TC, Berjanskii MV, Hau D, Li L, Huang A, Lee R, Gibbs E, Ladner C, Dong YW, Abera A, Cashman NR, Wishart DS FEBS J. 2011 Aug 16. doi: 10.1111/j.1742-4658.2011.08304.x. PMID:21848803[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Juanes ME, Elvira G, Garcia-Grande A, Calero M, Gasset M. Biosynthesis of prion protein nucleocytoplasmic isoforms by alternative initiation of translation. J Biol Chem. 2009 Jan 30;284(5):2787-94. doi: 10.1074/jbc.M804051200. Epub 2008, Dec 5. PMID:19059915 doi:10.1074/jbc.M804051200
- ↑ Perez-Pineiro R, Bjorndahl TC, Berjanskii MV, Hau D, Li L, Huang A, Lee R, Gibbs E, Ladner C, Dong YW, Abera A, Cashman NR, Wishart DS. The Prion Protein Binds Thiamine. FEBS J. 2011 Aug 16. doi: 10.1111/j.1742-4658.2011.08304.x. PMID:21848803 doi:10.1111/j.1742-4658.2011.08304.x
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