5yj5: Difference between revisions
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==structure for wildtype Human prion protein (M129)== | ==structure for wildtype Human prion protein (M129)== | ||
<StructureSection load='5yj5' size='340' side='right' caption='[[5yj5]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | <StructureSection load='5yj5' size='340' side='right'caption='[[5yj5]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5yj5]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YJ5 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5yj5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YJ5 FirstGlance]. <br> | ||
</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=5yj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yj5 OCA], [http://pdbe.org/5yj5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yj5 RCSB], [http://www.ebi.ac.uk/pdbsum/5yj5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yj5 ProSAT]</span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRNP, ALTPRP, PRIP, PRP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5yj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yj5 OCA], [http://pdbe.org/5yj5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yj5 RCSB], [http://www.ebi.ac.uk/pdbsum/5yj5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yj5 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/PRIO_HUMAN PRIO_HUMAN]] 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:12732622</ref> <ref>PMID:19936054</ref> <ref>PMID:20564047</ref> | [[http://www.uniprot.org/uniprot/PRIO_HUMAN PRIO_HUMAN]] 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:12732622</ref> <ref>PMID:19936054</ref> <ref>PMID:20564047</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Prion diseases are caused by the propagation of misfolded cellular prion proteins (PrPs). A completely prion disease-resistant genotype, V127M129, has been identified in Papua New Guinea and verified in transgenic mice. To disclose the structural basis of the disease-resistant effect of the G127V mutant, we determined and compared the structural and dynamic features of the G127V-mutated human PrP (residues 91-231) and the wild-type PrP in solution. HuPrP(G127V) contains alpha1, alpha2 and alpha3 helices and a stretch-strand (SS) pattern comprising residues Tyr128-Gly131 (SS1) and Val161-Arg164 (SS2), with extending atomic distances between the SS1 and SS2 strands, and a structural rearrangement of the Tyr128 side chain due to steric hindrance of the larger hydrophobic side chain of Val127. The extended alpha1 helix gets closer to the alpha2 and alpha3 helices. NMR dynamics analysis revealed that Tyr128, Gly131 and Tyr163 underwent significant conformational exchanges. Molecular dynamics simulations suggest that HuPrP(G127V) prevents the formation of stable beta-sheets and dimers. Unique structural and dynamic features potentially inhibit the conformational conversion of the G127V mutant. This work is beneficial for understanding the molecular mechanisms underlying the complete resistance of the G127V mutant to prion disease and for developing new therapeutics for prion disease. | |||
Structural basis for the complete resistance of the human prion protein mutant G127V to prion disease.,Zheng Z, Zhang M, Wang Y, Ma R, Guo C, Feng L, Wu J, Yao H, Lin D Sci Rep. 2018 Sep 4;8(1):13211. doi: 10.1038/s41598-018-31394-6. PMID:30181558<ref>PMID:30181558</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5yj5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Prion|Prion]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Lin, D]] | [[Category: Lin, D]] | ||
[[Category: Zheng, Z]] | [[Category: Zheng, Z]] | ||
[[Category: Membrane protein]] | [[Category: Membrane protein]] | ||
[[Category: Prion disease]] | [[Category: Prion disease]] | ||