000201198 001__ 201198
000201198 005__ 20240625095128.0
000201198 0247_ $$2doi$$a10.1021/bi2007564
000201198 0247_ $$2ISSN$$a0006-2960
000201198 0247_ $$2ISSN$$a1520-4995
000201198 0247_ $$2WOS$$aWOS:000293665500027
000201198 037__ $$aFZJ-2015-03503
000201198 082__ $$a570
000201198 1001_ $$0P:(DE-HGF)0$$aLosasso, Valeria$$b0
000201198 245__ $$aStructural Role of Compensatory Amino Acid Replacements in the α-Synuclein Protein
000201198 260__ $$aColumbus, Ohio$$bAmerican Chemical Society$$c2011
000201198 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1433939364_12150
000201198 3367_ $$2DataCite$$aOutput Types/Journal article
000201198 3367_ $$00$$2EndNote$$aJournal Article
000201198 3367_ $$2BibTeX$$aARTICLE
000201198 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000201198 3367_ $$2DRIVER$$aarticle
000201198 520__ $$aA subset of familial Parkinson’s disease (PD) cases is associated with the presence of disease-causing point mutations in human α-synuclein [huAS(wt)], including A53T. Surprisingly, the human neurotoxic amino acid 53T is present in non-primate, wild-type sequences of α-synucleins, including that expressed by mice [mAS(wt)]. Because huAS(A53T) causes neurodegeneration when expressed in rodents, the amino acid changes between the wild-type human protein [huAS(wt)] and mAS(wt) might act as intramolecular suppressors of A53T toxicity in the mouse protein, restoring its physiological structure and function. The lack of structural information for mAS(wt) in aqueous solution has prompted us to conduct a comparative molecular dynamics study of huAS(wt), huAS(A53T), and mAS(wt) in water at 300 K. The calculations are based on an ensemble of nuclear magnetic resonance-derived huAS(wt) structures. huAS(A53T) turns out to be more flexible and less compact than huAS(wt). Its central (NAC) region, involved in fibril formation by the protein, is more solvent-exposed than that of the wild-type protein, in agreement with nuclear magnetic resonance data. The compactness of mAS(wt) is similar to that of the human protein. In addition, its NAC region is less solvent-exposed and more rigid than that of huAS(A53T). All of these features may be caused by an increase in the level of intramolecular interactions on passing from huAS(A53T) to mAS(wt). We conclude that the presence of “compensatory replacements” in the mouse protein causes a significant change in the protein relative to huAS(A53T), restoring features not too dissimilar to those of the human protein.
000201198 536__ $$0G:(DE-HGF)POF2-899$$a899 - ohne Topic (POF2-899)$$cPOF2-899$$fPOF I$$x0
000201198 588__ $$aDataset connected to CrossRef, juser.fz-juelich.de
000201198 7001_ $$0P:(DE-HGF)0$$aPietropaolo, Adriana$$b1
000201198 7001_ $$0P:(DE-HGF)0$$aZannoni, Claudio$$b2
000201198 7001_ $$0P:(DE-HGF)0$$aGustincich, Stefano$$b3$$eCorresponding Author
000201198 7001_ $$0P:(DE-Juel1)145614$$aCarloni, Paolo$$b4$$eCorresponding Author$$ufzj
000201198 773__ $$0PERI:(DE-600)1472258-6$$a10.1021/bi2007564$$gVol. 50, no. 32, p. 6994 - 7001$$n32$$p6994 - 7001$$tBiochemistry$$v50$$x1520-4995$$y2011
000201198 8564_ $$uhttps://juser.fz-juelich.de/record/201198/files/bi2007564-1.pdf$$yRestricted
000201198 8564_ $$uhttps://juser.fz-juelich.de/record/201198/files/bi2007564-1.gif?subformat=icon$$xicon$$yRestricted
000201198 8564_ $$uhttps://juser.fz-juelich.de/record/201198/files/bi2007564-1.jpg?subformat=icon-1440$$xicon-1440$$yRestricted
000201198 8564_ $$uhttps://juser.fz-juelich.de/record/201198/files/bi2007564-1.jpg?subformat=icon-180$$xicon-180$$yRestricted
000201198 8564_ $$uhttps://juser.fz-juelich.de/record/201198/files/bi2007564-1.jpg?subformat=icon-640$$xicon-640$$yRestricted
000201198 8564_ $$uhttps://juser.fz-juelich.de/record/201198/files/bi2007564-1.pdf?subformat=pdfa$$xpdfa$$yRestricted
000201198 909CO $$ooai:juser.fz-juelich.de:201198$$pVDB
000201198 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR
000201198 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000201198 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000201198 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000201198 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000201198 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000201198 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000201198 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000201198 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000201198 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000201198 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF <  5
000201198 9101_ $$0I:(DE-588b)1026307295$$6P:(DE-HGF)0$$aGerman Research School for Simulation Sciences$$b0$$kGRS
000201198 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)145614$$aForschungszentrum Jülich GmbH$$b4$$kFZJ
000201198 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
000201198 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
000201198 920__ $$lyes
000201198 9201_ $$0I:(DE-Juel1)GRS-20100316$$kGRS$$lGRS$$x0
000201198 9201_ $$0I:(DE-Juel1)IAS-5-20120330$$kIAS-5$$lComputational Biomedicine$$x1
000201198 980__ $$ajournal
000201198 980__ $$aVDB
000201198 980__ $$aI:(DE-Juel1)GRS-20100316
000201198 980__ $$aI:(DE-Juel1)IAS-5-20120330
000201198 980__ $$aUNRESTRICTED
000201198 981__ $$aI:(DE-Juel1)INM-9-20140121
000201198 981__ $$aI:(DE-Juel1)IAS-5-20120330