Home > Publications database > Structural Role of Compensatory Amino Acid Replacements in the α-Synuclein Protein > print

001     201198
005     20240625095128.0
024 7 _ |2 doi
|a 10.1021/bi2007564
024 7 _ |2 ISSN
|a 0006-2960
024 7 _ |2 ISSN
|a 1520-4995
024 7 _ |2 WOS
|a WOS:000293665500027
037 _ _ |a FZJ-2015-03503
082 _ _ |a 570
100 1 _ |0 P:(DE-HGF)0
|a Losasso, Valeria
|b 0
245 _ _ |a Structural Role of Compensatory Amino Acid Replacements in the α-Synuclein Protein
260 _ _ |a Columbus, Ohio
|b American Chemical Society
|c 2011
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1433939364_12150
|2 PUB:(DE-HGF)
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|0 0
|2 EndNote
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a article
|2 DRIVER
520 _ _ |a A 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.
536 _ _ |0 G:(DE-HGF)POF2-899
|a 899 - ohne Topic (POF2-899)
|c POF2-899
|x 0
|f POF I
588 _ _ |a Dataset connected to CrossRef, juser.fz-juelich.de
700 1 _ |0 P:(DE-HGF)0
|a Pietropaolo, Adriana
|b 1
700 1 _ |0 P:(DE-HGF)0
|a Zannoni, Claudio
|b 2
700 1 _ |0 P:(DE-HGF)0
|a Gustincich, Stefano
|b 3
|e Corresponding Author
700 1 _ |0 P:(DE-Juel1)145614
|a Carloni, Paolo
|b 4
|e Corresponding Author
|u fzj
773 _ _ |0 PERI:(DE-600)1472258-6
|a 10.1021/bi2007564
|g Vol. 50, no. 32, p. 6994 - 7001
|n 32
|p 6994 - 7001
|t Biochemistry
|v 50
|x 1520-4995
|y 2011
856 4 _ |u https://juser.fz-juelich.de/record/201198/files/bi2007564-1.pdf
|y Restricted
856 4 _ |u https://juser.fz-juelich.de/record/201198/files/bi2007564-1.gif?subformat=icon
|x icon
|y Restricted
856 4 _ |u https://juser.fz-juelich.de/record/201198/files/bi2007564-1.jpg?subformat=icon-1440
|x icon-1440
|y Restricted
856 4 _ |u https://juser.fz-juelich.de/record/201198/files/bi2007564-1.jpg?subformat=icon-180
|x icon-180
|y Restricted
856 4 _ |u https://juser.fz-juelich.de/record/201198/files/bi2007564-1.jpg?subformat=icon-640
|x icon-640
|y Restricted
856 4 _ |u https://juser.fz-juelich.de/record/201198/files/bi2007564-1.pdf?subformat=pdfa
|x pdfa
|y Restricted
909 C O |o oai:juser.fz-juelich.de:201198
|p VDB
910 1 _ |0 I:(DE-588b)1026307295
|6 P:(DE-HGF)0
|a German Research School for Simulation Sciences
|b 0
|k GRS
910 1 _ |0 I:(DE-588b)5008462-8
|6 P:(DE-Juel1)145614
|a Forschungszentrum Jülich GmbH
|b 4
|k FZJ
913 2 _ |0 G:(DE-HGF)POF3-899
|1 G:(DE-HGF)POF3-890
|2 G:(DE-HGF)POF3-800
|a DE-HGF
|b Forschungsbereich Materie
|l Forschungsbereich Materie
|v ohne Topic
|x 0
913 1 _ |0 G:(DE-HGF)POF2-899
|1 G:(DE-HGF)POF2-890
|2 G:(DE-HGF)POF2-800
|a DE-HGF
|b Programmungebundene Forschung
|l ohne Programm
|v ohne Topic
|x 0
|4 G:(DE-HGF)POF
|3 G:(DE-HGF)POF2
915 _ _ |0 StatID:(DE-HGF)0100
|2 StatID
|a JCR
915 _ _ |0 StatID:(DE-HGF)0110
|2 StatID
|a WoS
|b Science Citation Index
915 _ _ |0 StatID:(DE-HGF)0111
|2 StatID
|a WoS
|b Science Citation Index Expanded
915 _ _ |0 StatID:(DE-HGF)0150
|2 StatID
|a DBCoverage
|b Web of Science Core Collection
915 _ _ |0 StatID:(DE-HGF)0199
|2 StatID
|a DBCoverage
|b Thomson Reuters Master Journal List
915 _ _ |0 StatID:(DE-HGF)0200
|2 StatID
|a DBCoverage
|b SCOPUS
915 _ _ |0 StatID:(DE-HGF)0300
|2 StatID
|a DBCoverage
|b Medline
915 _ _ |0 StatID:(DE-HGF)0310
|2 StatID
|a DBCoverage
|b NCBI Molecular Biology Database
915 _ _ |0 StatID:(DE-HGF)1030
|2 StatID
|a DBCoverage
|b Current Contents - Life Sciences
915 _ _ |0 StatID:(DE-HGF)1050
|2 StatID
|a DBCoverage
|b BIOSIS Previews
915 _ _ |0 StatID:(DE-HGF)9900
|2 StatID
|a IF < 5
920 _ _ |l yes
920 1 _ |0 I:(DE-Juel1)GRS-20100316
|k GRS
|l GRS
|x 0
920 1 _ |0 I:(DE-Juel1)IAS-5-20120330
|k IAS-5
|l Computational Biomedicine
|x 1
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a I:(DE-Juel1)GRS-20100316
980 _ _ |a I:(DE-Juel1)IAS-5-20120330
980 _ _ |a UNRESTRICTED
981 _ _ |a I:(DE-Juel1)INM-9-20140121
981 _ _ |a I:(DE-Juel1)IAS-5-20120330

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21