Core and heterogeneity of beta2-microglobulin amyloid fibrils as revealed by H/D exchange.
Dialysis-related amyloidosis, which occurs in the patients receiving a long-term hemodialysis with high frequency, accompanies the deposition of amyloid fibrils composed of beta(2)-microglobulin (beta2-m). In vitro, beta2-m forms two kinds of fibrous structures at acidic pH. One is a rigid "mature fibril", and the other is a flexible thin filament often called an "immature fibril". In addition, a 22-residue peptide (K3 peptide) corresponding to Ser20 to Lys41 of intact beta2-m forms rigid amyloid-like fibrils similar to mature fibrils. We compared the core of these three fibrils at single-residue resolution using a recently developed hydrogen/deuterium (H/D) exchange method with the dissolution of fibrils by dimethylsulfoxide (DMSO). The exchange time-course of these fibrils showed large deviations from a single exponential curve showing that, because of the supramolecular structures, the same residue exists in different environments from molecule to molecule, even in a single fibril. The exchange profiles revealed that the core of the immature fibril is restricted to a narrow region compared to that of the mature fibril. In contrast, all residues were protected from exchange in the K3 fibril, indicating that a whole region of the peptide is engaged in the beta-sheet network. These results suggest the mechanism of amyloid fibril formation, in which the core beta-sheet formed by a minimal sequence propagates to form a rigid and extensive beta-sheet network.
Yamaguchi
Kei-ichi
K
Institute for Protein Research, Osaka University and CREST, Japan Science and Technology Agency, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
Katou
Hidenori
H
Hoshino
Masaru
M
Hasegawa
Kazuhiro
K
Naiki
Hironobu
H
Goto
Yuji
Y
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D041961:Deuterium Exchange Measurement; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013057:Spectrum Analysis; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000378:metabolism*
D000682:Amyloid; D010455:Peptides; D001613:beta 2-Microglobulin