1fkc: Difference between revisions

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==HUMAN PRION PROTEIN (MUTANT E200K) FRAGMENT 90-231==
==HUMAN PRION PROTEIN (MUTANT E200K) FRAGMENT 90-231==
<StructureSection load='1fkc' size='340' side='right'caption='[[1fkc]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
<StructureSection load='1fkc' size='340' side='right'caption='[[1fkc]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1fkc]] 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=1FKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FKC FirstGlance]. <br>
<table><tr><td colspan='2'>[[1fkc]] 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=1FKC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FKC 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=1fkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fkc OCA], [http://pdbe.org/1fkc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fkc RCSB], [http://www.ebi.ac.uk/pdbsum/1fkc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1fkc ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 1 model</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=1fkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fkc OCA], [https://pdbe.org/1fkc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fkc RCSB], [https://www.ebi.ac.uk/pdbsum/1fkc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fkc ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[http://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:[http://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:[http://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:[http://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:[http://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:[http://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:[http://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 ==
[[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> 
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fk/1fkc_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fk/1fkc_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Soennichsen, F D]]
[[Category: Soennichsen FD]]
[[Category: Surewicz, W K]]
[[Category: Surewicz WK]]
[[Category: Swietnicki, W]]
[[Category: Swietnicki W]]
[[Category: Zagorski, M G]]
[[Category: Zagorski MG]]
[[Category: Zhang, Y]]
[[Category: Zhang Y]]
[[Category: Aggregation]]
[[Category: Creutzfeldt-jakob disease]]
[[Category: Membrane protein]]
[[Category: Prion]]
[[Category: Three helix]]

Latest revision as of 02:58, 21 November 2024

HUMAN PRION PROTEIN (MUTANT E200K) FRAGMENT 90-231HUMAN PRION PROTEIN (MUTANT E200K) FRAGMENT 90-231

Structural highlights

1fkc is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR, 1 model
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Prion propagation in transmissible spongiform encephalopathies involves the conversion of cellular prion protein, PrP(C), into a pathogenic conformer, PrP(Sc). Hereditary forms of the disease are linked to specific mutations in the gene coding for the prion protein. To gain insight into the molecular basis of these disorders, the solution structure of the familial Creutzfeldt-Jakob disease-related E200K variant of human prion protein was determined by multi-dimensional nuclear magnetic resonance spectroscopy. Remarkably, apart from minor differences in flexible regions, the backbone tertiary structure of the E200K variant is nearly identical to that reported for the wild-type human prion protein. The only major consequence of the mutation is the perturbation of surface electrostatic potential. The present structural data strongly suggest that protein surface defects leading to abnormalities in the interaction of prion protein with auxiliary proteins/chaperones or cellular membranes should be considered key determinants of a spontaneous PrP(C) --> PrP(Sc) conversion in the E200K form of hereditary prion disease.

Solution structure of the E200K variant of human prion protein. Implications for the mechanism of pathogenesis in familial prion diseases.,Zhang Y, Swietnicki W, Zagorski MG, Surewicz WK, Sonnichsen FD J Biol Chem. 2000 Oct 27;275(43):33650-4. PMID:10954699[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Zhang Y, Swietnicki W, Zagorski MG, Surewicz WK, Sonnichsen FD. Solution structure of the E200K variant of human prion protein. Implications for the mechanism of pathogenesis in familial prion diseases. J Biol Chem. 2000 Oct 27;275(43):33650-4. PMID:10954699 doi:10.1074/jbc.C000483200
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