title: SERF protein is a direct modifier of amyloid fiber assembly.
abstract: The inherent cytotoxicity of aberrantly folded protein aggregates contributes substantially to the pathogenesis of amyloid diseases. It was recently shown that a class of evolutionary conserved proteins, called MOAG-4/SERF, profoundly alter amyloid toxicity via an autonomous but yet unexplained mode. We show that the biological function of human SERF1a originates from its atypical ability to specifically distinguish between amyloid and nonamyloid aggregation. This inherently unstructured protein directly affected the aggregation kinetics of a broad range of amyloidogenic proteins in vitro, while being inactive against nonamyloid aggregation. A representative biophysical analysis of the SERF1a:α-synuclein (aSyn) complex revealed that the amyloid-promoting activity resulted from an early and transient interaction, which was sufficient to provoke a massive increase of soluble aSyn amyloid nucleation templates. Therefore, the autonomous amyloid-modifying activity of SERF1a observed in living organisms relies on a direct and dedicated manipulation of the early stages in the amyloid aggregation pathway.
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Austria. fabio.falsone@uni-graz.at
authors.forename: S Fabio
authors.initials: SF
authors.lastname: Falsone
authors.forename: N Helge
authors.initials: NH
authors.lastname: Meyer
authors.forename: Evelyne
authors.initials: E
authors.lastname: Schrank
authors.forename: Gerd
authors.initials: G
authors.lastname: Leitinger
authors.forename: Chi L L
authors.initials: CL
authors.lastname: Pham
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Fodero-Tavoletti
authors.forename: Mats
authors.initials: M
authors.lastname: Holmberg
authors.forename: Martin
authors.initials: M
authors.lastname: Dulle
authors.forename: Benjamin
authors.initials: B
authors.lastname: Scicluna
authors.forename: Bernd
authors.initials: B
authors.lastname: Gesslbauer
authors.forename: Hanna-Marie
authors.initials: HM
authors.lastname: Rückert
authors.forename: Gabriel E
authors.initials: GE
authors.lastname: Wagner
authors.forename: David A
authors.initials: DA
authors.lastname: Merle
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Nollen
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Kungl
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Hill
authors.forename: Roberto
authors.initials: R
authors.lastname: Cappai
authors.forename: Klaus
authors.initials: K
authors.lastname: Zangger
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D013552:Swine; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000682:Amyloid; D009419:Nerve Tissue Proteins; C114841:SERF1A protein, human; D051844:alpha-Synuclein