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== | ==Structure of an octapeptide repeat of the prion protein bound to the POM2 Fab antibody fragment== | ||
[[http://www.uniprot.org/uniprot/PRIO_MOUSE PRIO_MOUSE | <StructureSection load='4j8r' size='340' side='right'caption='[[4j8r]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4j8r]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J8R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J8R FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.303Å</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=4j8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j8r OCA], [https://pdbe.org/4j8r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j8r RCSB], [https://www.ebi.ac.uk/pdbsum/4j8r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j8r ProSAT]</span></td></tr> | |||
</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;"> | |||
== Publication Abstract from PubMed == | |||
Prion diseases are progressive, infectious neurodegenerative disorders caused primarily by the misfolding of the cellular prion protein (PrPc ) into an insoluble, protease-resistant, aggregated isoform termed PrPsc . In native conditions, PrPc has a structured C-terminal domain and a highly flexible N-terminal domain. A part of this N-terminal domain consists of 4-5 repeats of an unusual glycine-rich, eight amino acids long peptide known as the octapeptide repeat (OR) domain. In this article, we successfully report the first crystal structure of an OR of PrPc bound to the Fab fragment of the POM2 antibody. The structure was solved at a resolution of 2.3 A by molecular replacement. Although several studies have previously predicted a beta-turn-like structure of the unbound ORs, our structure shows an extended conformation of the OR when bound to a molecule of the POM2 Fab indicating that the bound Fab disrupts any putative native beta turn conformation of the ORs. Encouraging results from several recent studies have shown that administering small molecule ligands or antibodies targeting the OR domain of PrP result in arresting the progress of peripheral prion infections both in ex vivo and in in vivo models. This makes the structural study of the interactions of POM2 Fab with the OR domain very important as it would help us to design smaller and tighter binding OR ligands. | |||
The crystal structure of an octapeptide repeat of the Prion protein in complex with a Fab fragment of the POM2 antibody.,Swayampakula M, Baral PK, Aguzzi A, Kav NN, James MN Protein Sci. 2013 Apr 30. doi: 10.1002/pro.2270. PMID:23629842<ref>PMID:23629842</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4j8r" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Prion 3D structures|Prion 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Aguzzi | [[Category: Aguzzi A]] | ||
[[Category: Baral | [[Category: Baral PK]] | ||
[[Category: James | [[Category: James MNG]] | ||
[[Category: Kav | [[Category: Kav NNV]] | ||
[[Category: Swayampakula | [[Category: Swayampakula M]] | ||