title: The extreme N-terminal region of human apolipoprotein A-I has a strong propensity to form amyloid fibrils.
abstract: The N-terminal 1-83 residues of apolipoprotein A-I (apoA-I) have a strong propensity to form amyloid fibrils, in which the 46-59 segment was reported to aggregate to form amyloid-like fibrils. In this study, we demonstrated that a fragment peptide comprising the extreme N-terminal 1-43 residues strongly forms amyloid fibrils with a transition to β-sheet-rich structure, and that the G26R point mutation enhances the fibril formation of this segment. Our results suggest that in addition to the 46-59 segment, the extreme N-terminal region plays a crucial role in the development of amyloid fibrils by the N-terminal fragment of amyloidogenic apoA-I variants.
authors: Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
authors: Emi
authors: E
authors: Adachi
authors: Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
authors: Asako
authors: A
authors: Kosaka
authors: Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
authors: Kohei
authors: K
authors: Tsuji
authors: Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
authors: Chiharu
authors: C
authors: Mizuguchi
authors: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
authors: Hiroyuki
authors: H
authors: Kawashima
authors: Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
authors: Akira
authors: A
authors: Shigenaga
authors: Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
authors: Kohjiro
authors: K
authors: Nagao
authors: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
authors: Kenichi
authors: K
authors: Akaji
authors: Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
authors: Akira
authors: A
authors: Otaka
authors: Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505, Japan. Electronic address: hsaito@tokushima-u.ac.jp.
authors: Hiroyuki
authors: H
authors: Saito
mesh_terms: D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D002942:Circular Dichroism; D006801:Humans; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D017354:Point Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000682:Amyloid; D016632:Apolipoprotein A-I; D010446:Peptide Fragments
keywords: AFM; ATR; Amyloid fibril; Apolipoprotein A-I; FTIR; HDL; Peptide; Point mutation; ThT; WMF; apoA-I; apolipoprotein A-I; atomic force microscopy; attenuated total reflection; fourier transform infrared spectroscopy; high-density lipoprotein; thioflavinT; wavelength of maximum fluorescence