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| | ==Crystal structure of Syrian hamster prion protein complexed with POM1 FAB== | | ==Crystal structure of Syrian hamster prion protein complexed with POM1 FAB== |
| - | <StructureSection load='4yxl' size='340' side='right' caption='[[4yxl]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='4yxl' size='340' side='right'caption='[[4yxl]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yxl]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Golden_hamster Golden hamster] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YXL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YXL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yxl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mesocricetus_auratus Mesocricetus auratus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YXL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4yx2|4yx2]], [[4yxh|4yxh]]</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=4yxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yxl OCA], [https://pdbe.org/4yxl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yxl RCSB], [https://www.ebi.ac.uk/pdbsum/4yxl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yxl ProSAT]</span></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='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=4yxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yxl OCA], [http://pdbe.org/4yxl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yxl RCSB], [http://www.ebi.ac.uk/pdbsum/4yxl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yxl 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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| | </div> | | </div> |
| | <div class="pdbe-citations 4yxl" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4yxl" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Prion 3D structures|Prion 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Golden hamster]] | + | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mesocricetus auratus]] |
| - | [[Category: Baral, P K]] | + | [[Category: Mus musculus]] |
| - | [[Category: James, M N.G]] | + | [[Category: Baral PK]] |
| - | [[Category: Swayampakula, M]] | + | [[Category: James MNG]] |
| - | [[Category: Antibody]] | + | [[Category: Swayampakula M]] |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immune system complex]]
| + | |
| - | [[Category: Prion]]
| + | |
| 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
Misfolded prion proteins are the cause of neurodegenerative diseases that affect many mammalian species, including humans. Transmission of the prion diseases poses a considerable public-health risk as a specific prion disease such as bovine spongiform encephalopathy can be transferred to humans and other mammalian species upon contaminant exposure. The underlying mechanism of prion propagation and the species barriers that control cross species transmission has been investigated quite extensively. So far a number of prion strains have been characterized and those have been intimately linked to species-specific infectivity and other pathophysiological manifestations. These strains are encoded by a protein-only agent, and have a high degree of sequence identity across mammalian species. The molecular events that lead to strain differentiation remain elusive. In order to contribute to the understanding of strain differentiation, we have determined the crystal structures of the globular, folded domains of four prion proteins (cow, deer, elk and Syrian hamster) bound to the POM1 antibody fragment Fab. Although the overall structural folds of the mammalian prion proteins remains extremely similar, there are several local structural variations observed in the misfolding-initiator motifs. In additional molecular dynamics simulation studies on these several prion proteins reveal differences in the local fluctuations and imply that these differences have possible roles in the unfolding of the globular domains. These local variations in the structured domains perpetuate diverse patterns of prion misfolding and possibly facilitate the strain selection and adaptation.
X-ray structural and molecular dynamical studies of the globular domains of cow, deer, elk and Syrian hamster prion proteins.,Baral PK, Swayampakula M, Aguzzi A, James MN J Struct Biol. 2015 Oct;192(1):37-47. doi: 10.1016/j.jsb.2015.08.014. Epub 2015, Aug 28. PMID:26320075[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
- ↑ Baral PK, Swayampakula M, Aguzzi A, James MN. X-ray structural and molecular dynamical studies of the globular domains of cow, deer, elk and Syrian hamster prion proteins. J Struct Biol. 2015 Oct;192(1):37-47. doi: 10.1016/j.jsb.2015.08.014. Epub 2015, Aug 28. PMID:26320075 doi:http://dx.doi.org/10.1016/j.jsb.2015.08.014
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