title: Heparin promotes fibril formation by the N-terminal fragment of amyloidogenic apolipoprotein A-I.
abstract: Glycosaminoglycans are known to be associated with extracellular amyloid deposits of various amyloidogenic proteins. In this study, we found that the glycosaminoglycan heparin greatly accelerates the elongation step in fibril formation by the N-terminal 1-83 fragment of human apolipoprotein A-I (apoA-I), especially in the amyloidogenic W50R variant. Using fragment peptides, we demonstrate that heparin significantly promotes β-transition and fibril formation of the highly amyloidogenic region spanning residues 44-65 and colocalizes with fibrils formed by the W50R variant. These results suggest the possible role of glycosaminoglycans in fibril formation by amyloidogenic apoA-I variants.
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Japan.|Institute of Biomedical Sciences, Graduate School of Pharmaceutical Sciences, Tokushima University, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Mikawa
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Japan.|Institute of Biomedical Sciences, Graduate School of Pharmaceutical Sciences, Tokushima University, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Mizuguchi
authors.affiliation: Department of Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan.
authors.forename: Kazuchika
authors.initials: K
authors.lastname: Nishitsuji
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Baba
authors.affiliation: Institute of Biomedical Sciences, Graduate School of Pharmaceutical Sciences, Tokushima University, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shigenaga
authors.affiliation: Graduate School of Environmental and Life Science, Okayama University, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Shimanouchi
authors.affiliation: Department of Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakashita
authors.affiliation: Institute of Biomedical Sciences, Graduate School of Pharmaceutical Sciences, Tokushima University, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Otaka
authors.affiliation: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Akaji
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Japan. hsaito@mb.kyoto-phu.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Saito
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002942:Circular Dichroism; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D055550:Protein Stability; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: C505693:APOA1 protein, human; D000682:Amyloid; D016632:Apolipoprotein A-I; D010446:Peptide Fragments; D006493:Heparin
keywords: amyloid; apolipoprotein A-I; heparin