000827040 001__ 827040
000827040 005__ 20210129225738.0
000827040 0247_ $$2doi$$a10.1021/acs.jpcb.6b08485
000827040 0247_ $$2WOS$$aWOS:000390735800001
000827040 0247_ $$2altmetric$$aaltmetric:14720093
000827040 0247_ $$2pmid$$apmid:27934063
000827040 037__ $$aFZJ-2017-01246
000827040 082__ $$a530
000827040 1001_ $$0P:(DE-HGF)0$$aOrr, Asuka A.$$b0
000827040 245__ $$aUncovering the Binding and Specificity of β-Wrapins for Amyloid-β and α-Synuclein
000827040 260__ $$aWashington, DC$$bSoc.$$c2016
000827040 3367_ $$2DRIVER$$aarticle
000827040 3367_ $$2DataCite$$aOutput Types/Journal article
000827040 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1485866875_18211
000827040 3367_ $$2BibTeX$$aARTICLE
000827040 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000827040 3367_ $$00$$2EndNote$$aJournal Article
000827040 520__ $$aAmyloidogenic proteins amyloid-β peptide (Aβ) and α-synuclein (α-syn) self-assemble into fibrillar amyloid deposits, senile plaques and Lewy bodies, pathological features of Alzheimer’s and Parkinson’s diseases, respectively. Interestingly, a portion of Alzheimer’s disease cases also exhibit aggregation of α-syn into Lewy bodies, and growing evidence also suggests that Aβ and α-syn oligomers are toxic. Therefore, the simultaneous inhibition through sequestration of the two amyloidogenic proteins may constitute a promising therapeutic strategy. Recently discovered β-wrapin proteins pave the way toward this direction as they can inhibit the aggregation and toxicity of both Aβ and α-syn. Here, we used computational methods, primarily molecular dynamics simulations and free energy calculations, to shed light into the key interaction-based commonalities leading to the dual binding properties of β-wrapins for both amyloidogenic proteins, to identify which interactions potentially act as switches diminishing β-wrapins’ binding activity for Aβ/α-syn, and to examine the binding properties of the current most potent β-wrapin for Aβ. Our analysis provides insights into the distinct role of the key determinants leading to β-wrapin binding to Aβ and α-syn, and suggests that the Aβ 18VFFAED23 and α-syn 38LYVGSK43 are key domains determining the binding specificity of a β-wrapin. Our findings can potentially lead to the discovery of novel therapeutics for Alzheimer’s and Parkinson’s diseases.
000827040 536__ $$0G:(DE-HGF)POF3-553$$a553 - Physical Basis of Diseases (POF3-553)$$cPOF3-553$$fPOF III$$x0
000827040 7001_ $$0P:(DE-HGF)0$$aWördehoff$$b1
000827040 7001_ $$0P:(DE-Juel1)166306$$aHoyer, Wolfgang$$b2$$ufzj
000827040 7001_ $$0P:(DE-HGF)0$$aTamamis, Phanourios$$b3$$eCorresponding author
000827040 773__ $$0PERI:(DE-600)2006039-7$$a10.1021/acs.jpcb.6b08485$$n50$$p12781-12794$$tThe @journal of physical chemistry <Washington, DC> / B$$v120$$x1089-5647$$y2016
000827040 8564_ $$uhttps://juser.fz-juelich.de/record/827040/files/acs.jpcb.6b08485.pdf$$yRestricted
000827040 8564_ $$uhttps://juser.fz-juelich.de/record/827040/files/acs.jpcb.6b08485.gif?subformat=icon$$xicon$$yRestricted
000827040 8564_ $$uhttps://juser.fz-juelich.de/record/827040/files/acs.jpcb.6b08485.jpg?subformat=icon-1440$$xicon-1440$$yRestricted
000827040 8564_ $$uhttps://juser.fz-juelich.de/record/827040/files/acs.jpcb.6b08485.jpg?subformat=icon-180$$xicon-180$$yRestricted
000827040 8564_ $$uhttps://juser.fz-juelich.de/record/827040/files/acs.jpcb.6b08485.jpg?subformat=icon-640$$xicon-640$$yRestricted
000827040 8564_ $$uhttps://juser.fz-juelich.de/record/827040/files/acs.jpcb.6b08485.pdf?subformat=pdfa$$xpdfa$$yRestricted
000827040 909CO $$ooai:juser.fz-juelich.de:827040$$pVDB
000827040 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)166306$$aForschungszentrum Jülich$$b2$$kFZJ
000827040 9131_ $$0G:(DE-HGF)POF3-553$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lBioSoft – Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vPhysical Basis of Diseases$$x0
000827040 9141_ $$y2016
000827040 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000827040 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000827040 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences
000827040 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000827040 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000827040 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000827040 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000827040 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000827040 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ PHYS CHEM B : 2015
000827040 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000827040 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000827040 915__ $$0StatID:(DE-HGF)0550$$2StatID$$aNo Authors Fulltext
000827040 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000827040 920__ $$lyes
000827040 9201_ $$0I:(DE-Juel1)ICS-6-20110106$$kICS-6$$lStrukturbiochemie $$x0
000827040 980__ $$ajournal
000827040 980__ $$aVDB
000827040 980__ $$aUNRESTRICTED
000827040 980__ $$aI:(DE-Juel1)ICS-6-20110106
000827040 981__ $$aI:(DE-Juel1)IBI-7-20200312