title: Domain swapping in p13suc1 results in formation of native-like, cytotoxic aggregates.
abstract: The field of protein aggregation has been occupied mainly with the study of beta-strand self-association that occurs as a result of misfolding and leads to the formation of toxic protein aggregates and amyloid fibers. However, some of these aggregates retain native-like structural and enzymatic properties suggesting mechanisms other than beta-strand assembly. p13suc1 is a small protein that can exist as a monomer or a domain-swapped dimer. Here, we show that, under native conditions, p13suc1 forms three-dimensional domain-swapped aggregates, and that these aggregates are cytotoxic. Thus, toxicity of protein aggregates is not only associated with beta-rich assemblies and amyloid fibers, involving non-native interactions, but it can be induced by oligomeric misassembly that maintains predominantly native-like interactions.
authors.affiliation: SWITCH Laboratory, Flanders Institute for Biotechnology (VIB), Free University of Brussels, Pleinlaan 2, 1050 Brussels, Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Rousseau
authors.forename: Hannah
authors.initials: H
authors.lastname: Wilkinson
authors.forename: Josep
authors.initials: J
authors.lastname: Villanueva
authors.forename: Luis
authors.initials: L
authors.lastname: Serrano
authors.forename: Joost W H
authors.initials: JW
authors.lastname: Schymkowitz
authors.forename: Laura S
authors.initials: LS
authors.lastname: Itzhaki
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D003903:Deuterium / Q000378:metabolism; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D020673:Protein Renaturation; D017434:Protein Structure, Tertiary; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D018797:Cell Cycle Proteins; D029702:Schizosaccharomyces pombe Proteins; C051655:Suc1 protein, S pombe; D006859:Hydrogen; D003903:Deuterium