000172156 001__ 172156
000172156 005__ 20210129214400.0
000172156 0247_ $$2doi$$a10.1093/protein/gzu047
000172156 0247_ $$2WOS$$aWOS:000345837300002
000172156 037__ $$aFZJ-2014-05666
000172156 041__ $$aEnglish
000172156 082__ $$a540
000172156 1001_ $$0P:(DE-HGF)0$$aGauhar, Aziz$$b0
000172156 245__ $$aImpact of subunit linkages in an engineered homodimeric binding protein to α-synuclein
000172156 260__ $$aOxford$$bOxford Univ. Press$$c2014
000172156 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1416228091_11277
000172156 3367_ $$2DataCite$$aOutput Types/Journal article
000172156 3367_ $$00$$2EndNote$$aJournal Article
000172156 3367_ $$2BibTeX$$aARTICLE
000172156 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000172156 3367_ $$2DRIVER$$aarticle
000172156 520__ $$aAggregation of the protein α-synuclein (α-syn) has been implicated in Parkinson's disease and other neurodegenerative disorders, collectively referred to as synucleinopathies. The β-wrapin AS69 is a small engineered binding protein to α-syn that stabilizes a β-hairpin conformation of monomeric α-syn and inhibits α-syn aggregation at substoichiometric concentrations. AS69 is a homodimer whose subunits are linked via a disulfide bridge between their single cysteine residues, Cys-28. Here we show that expression of a functional dimer as a single polypeptide chain is achievable by head-to-tail linkage of AS69 subunits. Choice of a suitable linker is essential for construction of head-to-tail dimers that exhibit undiminished α-syn affinity compared with the solely disulfide-linked dimer. We characterize AS69-GS3, a head-to-tail dimer with a glycine-serine-rich linker, under oxidized and reduced conditions in order to evaluate the impact of the Cys28-disulfide bond on structure, stability and α-syn binding. Formation of the disulfide bond causes compaction of AS69-GS3, increases its thermostability, and is a prerequisite for high-affinity binding to α-syn. Comparison of AS69-GS3 and AS69 demonstrates that head-to-tail linkage promotes α-syn binding by affording accelerated disulfide bond formation.
000172156 536__ $$0G:(DE-HGF)POF2-453$$a453 - Physics of the Cell (POF2-453)$$cPOF2-453$$fPOF II$$x0
000172156 7001_ $$0P:(DE-HGF)0$$aShaykhalishahi, Hamed$$b1
000172156 7001_ $$0P:(DE-Juel1)145165$$aGremer, Lothar$$b2
000172156 7001_ $$0P:(DE-HGF)0$$aMirecka, Ewa$$b3
000172156 7001_ $$0P:(DE-HGF)0$$aHoyer, Wolfgang$$b4
000172156 773__ $$0PERI:(DE-600)1466729-0$$a10.1093/protein/gzu047$$n12$$p473-479$$tProtein engineering design and selection$$v27$$x0269-2139$$y2014
000172156 8564_ $$uhttp://peds.oxfordjournals.org/content/early/2014/10/20/protein.gzu047.long
000172156 8564_ $$uhttps://juser.fz-juelich.de/record/172156/files/FZJ-2014-05666.pdf$$yRestricted
000172156 909CO $$ooai:juser.fz-juelich.de:172156$$pVDB
000172156 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)145165$$aForschungszentrum Jülich GmbH$$b2$$kFZJ
000172156 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-HGF)0$$aForschungszentrum Jülich GmbH$$b4$$kFZJ
000172156 9132_ $$0G:(DE-HGF)POF3-553$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$aDE-HGF$$bPOF III$$lKey Technologies$$vBioSoft – Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$x0
000172156 9131_ $$0G:(DE-HGF)POF2-453$$1G:(DE-HGF)POF2-450$$2G:(DE-HGF)POF2-400$$3G:(DE-HGF)POF2$$4G:(DE-HGF)POF$$aDE-HGF$$bSchlüsseltechnologien$$lBioSoft$$vPhysics of the Cell$$x0
000172156 9141_ $$y2014
000172156 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR
000172156 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000172156 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000172156 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000172156 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000172156 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000172156 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000172156 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000172156 915__ $$0StatID:(DE-HGF)0400$$2StatID$$aAllianz-Lizenz / DFG
000172156 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000172156 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000172156 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000172156 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF <  5
000172156 920__ $$lyes
000172156 9201_ $$0I:(DE-Juel1)ICS-6-20110106$$kICS-6$$lStrukturbiochemie $$x0
000172156 980__ $$ajournal
000172156 980__ $$aVDB
000172156 980__ $$aI:(DE-Juel1)ICS-6-20110106
000172156 980__ $$aUNRESTRICTED
000172156 981__ $$aI:(DE-Juel1)IBI-7-20200312