title: What makes a protein sequence a prion?
abstract: Typical amyloid diseases such as Alzheimer's and Parkinson's were thought to exclusively result from de novo aggregation, but recently it was shown that amyloids formed in one cell can cross-seed aggregation in other cells, following a prion-like mechanism. Despite the large experimental effort devoted to understanding the phenomenon of prion transmissibility, it is still poorly understood how this property is encoded in the primary sequence. In many cases, prion structural conversion is driven by the presence of relatively large glutamine/asparagine (Q/N) enriched segments. Several studies suggest that it is the amino acid composition of these regions rather than their specific sequence that accounts for their priogenicity. However, our analysis indicates that it is instead the presence and potency of specific short amyloid-prone sequences that occur within intrinsically disordered Q/N-rich regions that determine their prion behaviour, modulated by the structural and compositional context. This provides a basis for the accurate identification and evaluation of prion candidate sequences in proteomes in the context of a unified framework for amyloid formation and prion propagation.
authors.affiliation: Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain; Institut de Nanociència i Nanotecnologia (IN2UB), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Raimon
authors.initials: R
authors.lastname: Sabate
authors.affiliation: VIB Switch Laboratory, VIB, Leuven, Belgium; Departement for Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Rousseau
authors.affiliation: VIB Switch Laboratory, VIB, Leuven, Belgium; Departement for Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Joost
authors.initials: J
authors.lastname: Schymkowitz
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Spain; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Ventura
mesh_terms: D000595:Amino Acid Sequence / Q000502:physiology*; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D011328:Prions / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D005656:Fungal Proteins; D011328:Prions