View source for 5yj4


==structure for the protective mutant G127V of Human prion protein==
<StructureSection load='5yj4' size='340' side='right'caption='[[5yj4]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5yj4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YJ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YJ4 FirstGlance]. <br>
</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=5yj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yj4 OCA], [https://pdbe.org/5yj4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yj4 RCSB], [https://www.ebi.ac.uk/pdbsum/5yj4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yj4 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> 
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Prion 3D structures|Prion 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Lin D]]
[[Category: Zheng Z]]