Analysis of Amyloid Beta 1-16 (A beta 16) Monomer and Dimer Using Electrospray Ionization Mass Spectrometry with Collision-Induced Dissociation

Abstract

The monomer and dimer structures of the amyloid fragment A beta(1-16) sequence formed in H2O were investigated using electrospray ionization mass spectrometry (MS) and tandem MS (MS/MS). A beta 16 monomers and dimers were indicated by signals representing multiple proton adduct forms, [monomer+zH](n+) (=Mz+, z = charge state) and [dimer+zH](z+) (=Dz+), in the MS spectrum. Fragment ions of monomers and dimers were observed using collision-induced dissociation MS/MS. Peptide bond dissociation was mostly observed in the D1-D7 and V11-K16 regions of the MS/MS spectra for the monomer (or dimer), regardless of the monomer (or dimer) charge state. Both covalent and non-covalent bond dissociation processes were indicated by the MS/MS results for the dimers. During the non-covalent bond dissociation process, the D3+ dimer complex was separated into two components: the M1+ and M2+ subunits. During the covalent bond dissociation of the D3+ dimer complex, the b and y fragment ions attached to the monomer, (M+b(10-15))(z+) and (M+y(9-15))(z+), were thought to originate from the dissociation of the M2+ monomer component of the (M1++M2+) complex. Two different D3+ complex geometries exist; two distinguished interaction geometries resulting from interactions between the M1+ monomer and two different regions of M2+ (the N-terminus and C-terminus) are proposed. Intricate fragmentation patterns were observed in the MS/MS spectrum of the D5+ complex. The complicated nature of the MS/MS spectrum is attributable to the coexistence of two D5+ configurations, (M1+ +M4+) and (M2+ + M3+), in the A beta 16 solution.