View source for 1oei


==Human prion protein 61-84==
<StructureSection load='1oei' size='340' side='right'caption='[[1oei]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1oei]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The May 2008 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Prions''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2008_5 10.2210/rcsb_pdb/mom_2008_5]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OEI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OEI FirstGlance]. <br>
</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'>[https://proteopedia.org/fgij/fg.htm?mol=1oei FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oei OCA], [https://pdbe.org/1oei PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oei RCSB], [https://www.ebi.ac.uk/pdbsum/1oei PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oei ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PRIO_HUMAN PRIO_HUMAN] Note=PrP is found in high quantity in the brain of humans and animals infected with neurodegenerative diseases known as transmissible spongiform encephalopathies or prion diseases, like: Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI), Gerstmann-Straussler disease (GSD), Huntington disease-like type 1 (HDL1) and kuru in humans; scrapie in sheep and goat; bovine spongiform encephalopathy (BSE) in cattle; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of mule deer and elk; feline spongiform encephalopathy (FSE) in cats and exotic ungulate encephalopathy (EUE) in nyala and greater kudu. The prion diseases illustrate three manifestations of CNS degeneration: (1) infectious (2) sporadic and (3) dominantly inherited forms. TME, CWD, BSE, FSE, EUE are all thought to occur after consumption of prion-infected foodstuffs.<ref>PMID:19936054</ref> <ref>PMID:1671440</ref> <ref>PMID:1975028</ref> <ref>PMID:8461023</ref> <ref>PMID:7902693</ref> <ref>PMID:7906019</ref> <ref>PMID:7913755</ref> <ref>PMID:8909447</ref> <ref>PMID:9266722</ref> <ref>PMID:10790216</ref>   Defects in PRNP are the cause of Creutzfeldt-Jakob disease (CJD) [MIM:[https://omim.org/entry/123400 123400]. CJD occurs primarily as a sporadic disorder (1 per million), while 10-15% are familial. Accidental transmission of CJD to humans appears to be iatrogenic (contaminated human growth hormone (HGH), corneal transplantation, electroencephalographic electrode implantation, etc.). Epidemiologic studies have failed to implicate the ingestion of infected annimal meat in the pathogenesis of CJD in human. The triad of microscopic features that characterize the prion diseases consists of (1) spongiform degeneration of neurons, (2) severe astrocytic gliosis that often appears to be out of proportion to the degree of nerve cell loss, and (3) amyloid plaque formation. CJD is characterized by progressive dementia and myoclonic seizures, affecting adults in mid-life. Some patients present sleep disorders, abnormalities of high cortical function, cerebellar and corticospinal disturbances. The disease ends in death after a 3-12 months illness.<ref>PMID:19936054</ref> <ref>PMID:1671440</ref> <ref>PMID:1975028</ref> <ref>PMID:8461023</ref> <ref>PMID:7902693</ref> <ref>PMID:7906019</ref> <ref>PMID:7913755</ref> <ref>PMID:8909447</ref> <ref>PMID:9266722</ref> <ref>PMID:10790216</ref>   Defects in PRNP are the cause of fatal familial insomnia (FFI) [MIM:[https://omim.org/entry/600072 600072]. FFI is an autosomal dominant disorder and is characterized by neuronal degeneration limited to selected thalamic nuclei and progressive insomnia.<ref>PMID:19936054</ref> <ref>PMID:19927125</ref> <ref>PMID:1347910</ref>   Defects in PRNP are the cause of Gerstmann-Straussler disease (GSD) [MIM:[https://omim.org/entry/137440 137440]. GSD is a heterogeneous disorder and was defined as a spinocerebellar ataxia with dementia and plaquelike deposits. GSD incidence is less than 2 per 100 million live births.<ref>PMID:19936054</ref> <ref>PMID:19927125</ref> <ref>PMID:10581485</ref> <ref>PMID:2564168</ref> <ref>PMID:1363810</ref> <ref>PMID:7902972</ref> <ref>PMID:7699395</ref> <ref>PMID:7783876</ref> <ref>PMID:8797472</ref> <ref>PMID:9786248</ref> <ref>PMID:11709001</ref>   Defects in PRNP are the cause of Huntington disease-like type 1 (HDL1) [MIM:[https://omim.org/entry/603218 603218]. HDL1 is an autosomal dominant, early onset neurodegenerative disorder with prominent psychiatric features.<ref>PMID:19936054</ref>   Defects in PRNP are the cause of kuru (KURU) [MIM:[https://omim.org/entry/245300 245300]. Kuru is transmitted during ritualistic cannibalism, among natives of the New Guinea highlands. Patients exhibit various movement disorders like cerebellar abnormalities, rigidity of the limbs, and clonus. Emotional lability is present, and dementia is conspicuously absent. Death usually occurs from 3 to 12 month after onset.<ref>PMID:19936054</ref>   Defects in PRNP are the cause of spongiform encephalopathy with neuropsychiatric features (SENF) [MIM:[https://omim.org/entry/606688 606688]; an autosomal dominant presenile dementia with a rapidly progressive and protracted clinical course. The dementia was characterized clinically by frontotemporal features, including early personality changes. Some patients had memory loss, several showed aggressiveness, hyperorality and verbal stereotypy, others had parkinsonian symptoms.<ref>PMID:19936054</ref> 
== Function ==
[https://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 ==
Structural studies of mammalian prion protein at pH values between 4.5 and 5.5 established that the N-terminal 100 residue domain is flexibly disordered. Here, we show that at pH values between 6.5 and 7.8, i.e. the pH at the cell membrane, the octapeptide repeats in recombinant human prion protein hPrP(23-230) encompassing the highly conserved amino acid sequence PHGGGWGQ are structured. The nuclear magnetic resonance solution structure of the octapeptide repeats at pH 6.2 reveals a new structural motif that causes a reversible pH-dependent PrP oligomerization. Within the aggregation motif the segments HGGGW and GWGQ adopt a loop conformation and a beta-turn-like structure, respectively. Comparison with the crystal structure of HGGGW-Cu(2+) indicates that the binding of copper ions induces a conformational transition that presumably modulates PrP aggregation. The knowledge that the cellular prion protein is immobilized on the cell surface along with our results suggests a functional role of aggregation in endocytosis or homophilic cell adhesion.

The octapeptide repeats in mammalian prion protein constitute a pH-dependent folding and aggregation site.,Zahn R J Mol Biol. 2003 Nov 28;334(3):477-88. PMID:14623188<ref>PMID:14623188</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1oei" style="background-color:#fffaf0;"></div>

==See Also==
*[[Prion 3D structures|Prion 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Prions]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Zahn R]]