title: Amyloidogenic synthetic peptides of beta2-microglobulin--a role of the disulfide bond.
abstract: To search for the essential regions responsible for the beta2-microglobulin (beta2-m) amyloid fibril formation, we synthesized six peptides corresponding to six of the seven beta-sheets in the native structure of beta2-m, and examined their amyloidogenicity. Among the peptides examined, peptide (21-31) (strand B) and the mixture of peptide (21-31) and (78-86) (strand F) showed fibril formation at both pH 2.5 and 7.5. Peptide (21-31) is the N-terminal half of the previously reported proteolytic fragment of beta2-m, Ser21-Lys41 (K3), suggesting that this region may be the essential core. Interestingly, the dimer formation of peptide (21-31) by the disulfide bond substantially facilitated the fibril formation, indicating that the disulfide bond is important for the structural stability of the fibrils.
authors.affiliation: Department of Pathology, Fukui Medical University, 910-1193, Fukui, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ohhashi
authors.forename: Itaru
authors.initials: I
authors.lastname: Yamaguchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Shinobu
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
authors.forename: Fumitake
authors.initials: F
authors.lastname: Gejyo
authors.forename: Hironobu
authors.initials: H
authors.lastname: Naiki
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000737:chemistry*; D004229:Dithiothreitol / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D017384:Sequence Deletion; D001613:beta 2-Microglobulin / Q000737:chemistry*
chemical_list: D000682:Amyloid; D004220:Disulfides; D010455:Peptides; D001613:beta 2-Microglobulin; D004229:Dithiothreitol