Amyloidogenic synthetic peptides of beta2-microglobulin--a role of the disulfide bond.
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.
Hasegawa
Kazuhiro
K
Department of Pathology, Fukui Medical University, 910-1193, Fukui, Japan.
Ohhashi
Yumiko
Y
Yamaguchi
Itaru
I
Takahashi
Naoki
N
Tsutsumi
Shinobu
S
Goto
Yuji
Y
Gejyo
Fumitake
F
Naiki
Hironobu
H
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*
D000682:Amyloid; D004220:Disulfides; D010455:Peptides; D001613:beta 2-Microglobulin; D004229:Dithiothreitol