Analysis of oligomeric complexes of the amyloid-forming FYLLYY peptide by collision-induced dissociation with electrospray ionization mass spectrometry

Abstract

The monomeric and oligomeric structures of the "FYLLYY" β₂ microglobulin (β₂m) active sequence, formed in (DMSO/CH₃CN) solution, were investigated using electrospray ionization (ESI) mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Dissociation of dimer and trimer ions was investigated by tandem mass spectrometry using collision induced dissociation (CID). The covalent bond fragmentation patterns were observed in the 2¹⁺ and 3²⁺ MS/MS spectra (2¹⁺ = [dimer+H]¹⁺ and 3²⁺ = [trimer + 2H]²⁺). A π-π stacking geometry for the FYLLYY 2¹⁺ complex and partial parallel β-sheet geometry for the 3²⁺ complex are proposed to be stable structures. The observed covalent bond fragment ions in the MS/MS spectra of the 3²⁺ complex are considered to have originated from the partial parallel β-sheet moiety. The FYLLYY → AALLGY (or FYLLAA) substituted sequence was also investigated by CID-MS/MS. Our MS/MS analysis suggests that the π-π stacking interaction structures are important in dimer binding rather than the structures of a complete parallel or anti-parallel β-sheet 2¹⁺ complex.

Keywords: FYLLYY; MS/MS; Peptide dimer; mass spectrometry (MS); peptide oligomer.