title: Polyalanine-independent conformational conversion of nuclear poly(A)-binding protein 1 (PABPN1).
abstract: Oculopharyngeal muscular dystrophy is a late-onset disease caused by an elongation of a natural 10-alanine segment within the N-terminal domain of the nuclear poly(A)-binding protein 1 (PABPN1) to maximally 17 alanines. The disease is characterized by intranuclear deposits consisting primarily of PABPN1. In previous studies, we could show that the N-terminal domain of PABPN1 forms amyloid-like fibrils. Here, we analyze fibril formation of full-length PABPN1. Unexpectedly, fibril formation was independent of the presence of the alanine segment. With regard to fibril formation kinetics and resistance against denaturants, fibrils formed by full-length PABPN1 had completely different properties from those formed by the N-terminal domain. Fourier transformed infrared spectroscopy and limited proteolysis showed that fibrillar PABPN1 has a structure that differs from native PABPN1. Circumstantial evidence is presented that the C-terminal domain is involved in fibril formation.
authors.affiliation: Institute for Biochemistry and Biotechnology, Technical Biochemistry, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany.
authors.forename: Reno
authors.initials: R
authors.lastname: Winter
authors.forename: Uwe
authors.initials: U
authors.lastname: Kühn
authors.forename: Gerd
authors.initials: G
authors.lastname: Hause
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schwarz
mesh_terms: D000409:Alanine / Q000737:chemistry; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D039141:Muscular Dystrophy, Oculopharyngeal / Q000235:genetics* / Q000378:metabolism; D039103:Poly(A)-Binding Protein II / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D057165:Proteostasis Deficiencies / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D013055:Spectrophotometry, Infrared
chemical_list: D039103:Poly(A)-Binding Protein II; D011994:Recombinant Proteins; D000409:Alanine