000201265 001__ 201265
000201265 005__ 20240625095111.0
000201265 0247_ $$2doi$$a10.1002/prot.22834
000201265 0247_ $$2ISSN$$a0887-3585
000201265 0247_ $$2ISSN$$a1097-0134
000201265 0247_ $$2WOS$$aWOS:000284046400003
000201265 037__ $$aFZJ-2015-03570
000201265 082__ $$a540
000201265 1001_ $$0P:(DE-Juel1)145921$$aRossetti, Giulia$$b0$$ufzj
000201265 245__ $$aStructural facets of disease-linked human prion protein mutants: A molecular dynamic study
000201265 260__ $$aNew York, NY$$bWiley-Liss$$c2010
000201265 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1433834467_26780
000201265 3367_ $$2DataCite$$aOutput Types/Journal article
000201265 3367_ $$00$$2EndNote$$aJournal Article
000201265 3367_ $$2BibTeX$$aARTICLE
000201265 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000201265 3367_ $$2DRIVER$$aarticle
000201265 520__ $$aPrion propagation in transmissible spongiform encephalopathies involves the conversion of the cellular prion protein, PrPC, into the pathogenic conformer PrPSc. Human familial forms of the disease are linked to specific mutations in the PrP gene, PRNP, and include Gerstmann-Sträussler-Scheinker syndrome (GSS), familial Creutzfeldt-Jakob disease (fCJD), and fatal familial insomnia. To gain insights into the molecular basis of these disorders, we performed 200 ns of classical molecular dynamic simulations in aqueous solution on wild type (WT) human PrP (HuPrP), and on three HuPrP variants located in the globular HuPrP domain: two pathological mutations, HuPrP(Q212P) and HuPrP(E200K), linked to GSS and to fCJD respectively, and one protective polymorphism, HuPrP(E219K) (total time-scale simulated 800 ns). A comparison between the predicted structural determinants of WT HuPrP and HuPrP(E200K) with their NMR structures established the accuracy of the methods used. Strikingly, the analyzed disease-linked variants produced their major effect on the α2-α3 region and the β2-α2 loop, regardless of the mutation position. The conformational change of the latter might affect the interactions with cellular partners in the fibrillation process. The protocol proposed here represents a powerful approach for reproducing the structural effects of genetic mutations located in the globular domain of HuPrP, such as the GSS-related HuPrP(Q212P) and the protective polymorphism HuPrP(E219K).
000201265 536__ $$0G:(DE-HGF)POF2-899$$a899 - ohne Topic (POF2-899)$$cPOF2-899$$fPOF I$$x0
000201265 588__ $$aDataset connected to CrossRef, juser.fz-juelich.de
000201265 7001_ $$0P:(DE-HGF)0$$aGiachin, Gabriele$$b1
000201265 7001_ $$0P:(DE-HGF)0$$aLegname, Giuseppe$$b2
000201265 7001_ $$0P:(DE-Juel1)145614$$aCarloni, Paolo$$b3$$eCorresponding Author$$ufzj
000201265 773__ $$0PERI:(DE-600)1475032-6$$a10.1002/prot.22834$$gVol. 78, no. 16, p. 3270 - 3280$$n16$$p3270 - 3280$$tProteins$$v78$$x0887-3585$$y2010
000201265 8564_ $$uhttps://juser.fz-juelich.de/record/201265/files/22834_ftp.pdf$$yRestricted
000201265 8564_ $$uhttps://juser.fz-juelich.de/record/201265/files/22834_ftp.gif?subformat=icon$$xicon$$yRestricted
000201265 8564_ $$uhttps://juser.fz-juelich.de/record/201265/files/22834_ftp.jpg?subformat=icon-1440$$xicon-1440$$yRestricted
000201265 8564_ $$uhttps://juser.fz-juelich.de/record/201265/files/22834_ftp.jpg?subformat=icon-180$$xicon-180$$yRestricted
000201265 8564_ $$uhttps://juser.fz-juelich.de/record/201265/files/22834_ftp.jpg?subformat=icon-640$$xicon-640$$yRestricted
000201265 8564_ $$uhttps://juser.fz-juelich.de/record/201265/files/22834_ftp.pdf?subformat=pdfa$$xpdfa$$yRestricted
000201265 909CO $$ooai:juser.fz-juelich.de:201265$$pVDB
000201265 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR
000201265 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000201265 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000201265 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000201265 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000201265 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000201265 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000201265 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000201265 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000201265 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000201265 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF <  5
000201265 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)145921$$aForschungszentrum Jülich GmbH$$b0$$kFZJ
000201265 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)145614$$aForschungszentrum Jülich GmbH$$b3$$kFZJ
000201265 9132_ $$0G:(DE-HGF)POF3-899$$1G:(DE-HGF)POF3-890$$2G:(DE-HGF)POF3-800$$aDE-HGF$$bForschungsbereich Materie$$lForschungsbereich Materie$$vohne Topic$$x0
000201265 9131_ $$0G:(DE-HGF)POF2-899$$1G:(DE-HGF)POF2-890$$2G:(DE-HGF)POF2-800$$3G:(DE-HGF)POF2$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0
000201265 920__ $$lyes
000201265 9201_ $$0I:(DE-Juel1)GRS-20100316$$kGerman Research School for Simulation Sciences (GRS)$$lGRS$$x0
000201265 9201_ $$0I:(DE-Juel1)IAS-5-20120330$$kIAS-5$$lComputational Biomedicine$$x1
000201265 980__ $$ajournal
000201265 980__ $$aVDB
000201265 980__ $$aI:(DE-Juel1)GRS-20100316
000201265 980__ $$aI:(DE-Juel1)IAS-5-20120330
000201265 980__ $$aUNRESTRICTED
000201265 981__ $$aI:(DE-Juel1)INM-9-20140121
000201265 981__ $$aI:(DE-Juel1)IAS-5-20120330