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| | ==NMR structure of the octarepeat region of prion protein bound to pentosan polysulfate== | | ==NMR structure of the octarepeat region of prion protein bound to pentosan polysulfate== |
| - | <StructureSection load='2kkg' size='340' side='right' caption='[[2kkg]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kkg' size='340' side='right'caption='[[2kkg]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kkg]] 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=2KKG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KKG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kkg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mesocricetus_auratus Mesocricetus auratus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KKG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KKG FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2kkg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kkg OCA], [http://pdbe.org/2kkg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kkg RCSB], [http://www.ebi.ac.uk/pdbsum/2kkg PDBsum]</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=2kkg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kkg OCA], [https://pdbe.org/2kkg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kkg RCSB], [https://www.ebi.ac.uk/pdbsum/2kkg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kkg 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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kk/2kkg_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kk/2kkg_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kkg ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | ==See Also== | | ==See Also== |
| - | *[[Prion|Prion]] | + | *[[Prion 3D structures|Prion 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Golden hamster]] | + | [[Category: Large Structures]] |
| - | [[Category: Caughey, B]] | + | [[Category: Mesocricetus auratus]] |
| - | [[Category: Copie, V]] | + | [[Category: Caughey B]] |
| - | [[Category: Taubner, L M]] | + | [[Category: Copie V]] |
| - | [[Category: Cell membrane]] | + | [[Category: Taubner LM]] |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Golgi apparatus]]
| + | |
| - | [[Category: Gpi-anchor]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Octapeptide repeat]]
| + | |
| - | [[Category: Pentosan polysulfate]]
| + | |
| - | [[Category: Prion]]
| + | |
| - | [[Category: Prion protein]]
| + | |
| - | [[Category: Sulfated glycan]]
| + | |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The intrinsically disordered amino-proximal domain of hamster prion protein (PrP) contains four copies of a highly conserved octapeptide sequence, PHGGGWGQ, that is flanked by two polycationic residue clusters. This N-terminal domain mediates the binding of sulfated glycans, which can profoundly influence the conversion of PrP to pathological forms and the progression of prion disease. To investigate the structural consequences of sulfated glycan binding, we performed multidimensional heteronuclear ((1)H, (13)C, (15)N) NMR (nuclear magnetic resonance), circular dichroism (CD), and fluorescence studies on hamster PrP residues 23-106 (PrP 23-106) and fragments thereof when bound to pentosan polysulfate (PPS). While the majority of PrP 23-106 remain disordered upon PPS binding, the octarepeat region adopts a repeating loop-turn structure that we have determined by NMR. The beta-like turns within the repeats are corroborated by CD data demonstrating that these turns are also present, although less pronounced, without PPS. Binding to PPS exposes a hydrophobic surface composed of aligned tryptophan side chains, the spacing and orientation of which are consistent with a self-association or ligand binding site. The unique tryptophan motif was probed by intrinsic tryptophan fluorescence, which displayed enhanced fluorescence of PrP 23-106 when bound to PPS, consistent with the alignment of tryptophan side chains. Chemical-shift mapping identified binding sites on PrP 23-106 for PPS, which include the octarepeat histidine and an N-terminal basic cluster previously linked to sulfated glycan binding. These data may in part explain how sulfated glycans modulate PrP conformational conversions and oligomerizations.
Structure of the flexible amino-terminal domain of prion protein bound to a sulfated glycan.,Taubner LM, Bienkiewicz EA, Copie V, Caughey B J Mol Biol. 2010 Jan 22;395(3):475-90. Epub 2009 Nov 10. PMID:19913031[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
- ↑ Taubner LM, Bienkiewicz EA, Copie V, Caughey B. Structure of the flexible amino-terminal domain of prion protein bound to a sulfated glycan. J Mol Biol. 2010 Jan 22;395(3):475-90. Epub 2009 Nov 10. PMID:19913031 doi:10.1016/j.jmb.2009.10.075
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