title: Bacterial Chaperones CsgE and CsgC Differentially Modulate Human α-Synuclein Amyloid Formation via Transient Contacts.
abstract: Amyloid formation is historically associated with cytotoxicity, but many organisms produce functional amyloid fibers (e.g., curli) as a normal part of cell biology. Two E. coli genes in the curli operon encode the chaperone-like proteins CsgC and CsgE that both can reduce in vitro amyloid formation by CsgA. CsgC was also found to arrest amyloid formation of the human amyloidogenic protein α-synuclein, which is involved in Parkinson's disease. Here, we report that the inhibitory effects of CsgC arise due to transient interactions that promote the formation of spherical α-synuclein oligomers. We find that CsgE also modulates α-synuclein amyloid formation through transient contacts but, in contrast to CsgC, CsgE accelerates α-synuclein amyloid formation. Our results demonstrate the significance of transient protein interactions in amyloid regulation and emphasize that the same protein may inhibit one type of amyloid while accelerating another.
authors.affiliation: Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Chorell
authors.affiliation: Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Andersson
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Margery L
authors.initials: ML
authors.lastname: Evans
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Neha
authors.initials: N
authors.lastname: Jain
authors.affiliation: Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Götheson
authors.affiliation: Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Åden
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Chapman
authors.affiliation: Department of Chemistry, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research, Umeå University, Umeå, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Almqvist
authors.affiliation: Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wittung-Stafshede
mesh_terms: D000818:Animals; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D066263:Protein Aggregation, Pathological; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C556817:CsgC protein, E coli; C561979:CsgE protein, E coli; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D051844:alpha-Synuclein