The role of disulfide bond in the amyloidogenic state of β2‐microglobulin studied by heteronuclear NMR

• DOI: 10.1110/ps.0213202
• Publication Date: 2002-10-01T19:26:48Z
• Authors: Hidenori Katou; Takashi Kanno; Masaru Hoshino; Yoshihisa Hagihara; Hiroyuki Tanaka; Tomoji Kawai; Kazuhiro Hasegawa; Hironobu Naiki; Yuji Goto
• Keywords: Heteronuclear molecule

beta(2)-Microglobulin (beta2-m) is a major component of dialysis-related amyloid fibrils. Although recombinant beta2-m forms needle-like fibrils by in vitro extension reaction at pH 2.5, reduced beta2-m, which the intrachain disulfide bond reduced, cannot form typical Instead, thinner and flexible filaments are formed, as shown atomic force microscopy images. To clarify role fibril formation, we characterized conformations oxidized (intact) acid-denatured state well native 6.5, heteronuclear NMR. [(1)H]-(15)N NOE regions between two cysteine residues (Cys25-Cys80) revealed marked difference pico- nanosecond time scale dynamics that states, with former showing mobility. Intriguingly, secondary chemical shifts, DeltaCalpha, DeltaCO, DeltaHalpha, (3)J(HNHalpha) coupling constants indicated both 2.5 have marginal alpha-helical propensity close to C-terminal cysteine, although it beta-sheet protein state. The results suggest mobility denatured an important factor for amylodogenic potential helical might play modifying this potential.