title: Mechanisms of amyloid fibril formation--focus on domain-swapping.
abstract: Conformational diseases constitute a group of heterologous disorders in which a constituent host protein undergoes changes in conformation, leading to aggregation and deposition. To understand the molecular mechanisms of the process of amyloid fibril formation, numerous in vitro and in vivo studies, including model and pathologically relevant proteins, have been performed. Understanding the molecular details of these processes is of major importance to understand neurodegenerative diseases and could contribute to more effective therapies. Many models have been proposed to describe the mechanism by which proteins undergo ordered aggregation into amyloid fibrils. We classify these as: (a) templating and nucleation; (b) linear, colloid-like assembly of spherical oligomers; and (c) domain-swapping. In this review, we stress the role of domain-swapping and discuss the role of proline switches.
authors.affiliation: Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, Ljubljana, Slovenia. eva.zerovnik@ijs.si
authors.forename: Eva
authors.initials: E
authors.lastname: Žerovnik
authors.forename: Veronika
authors.initials: V
authors.lastname: Stoka
authors.forename: Andreja
authors.initials: A
authors.lastname: Mirtič
authors.forename: Gregor
authors.initials: G
authors.lastname: Gunčar
authors.forename: Jože
authors.initials: J
authors.lastname: Grdadolnik
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Staniforth
authors.forename: Dušan
authors.initials: D
authors.lastname: Turk
authors.forename: Vito
authors.initials: V
authors.lastname: Turk
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008958:Models, Molecular; D011392:Proline / Q000737:chemistry*; D017434:Protein Structure, Tertiary
chemical_list: D000682:Amyloid; D011392:Proline