Multiply charged oligomer complexes composed of the amyloid-forming peptides NNQQNY, VQIVYK, and LYQLEN analyzed by collision-induced dissociation with electrospray ionization mass spectroscopy

Abstract Recent research has implicated small, toxic, insoluble oligomeric assemblies as factors in amyloidogenic diseases, but information regarding their biological features, structures, and formation mechanisms has been difficult to obtain. Many shorter but biologically active sequences have also been identified in the larger sequences of amyloid proteins that are themselves capable of forming amyloid fibrils. Here, we used collision-induced dissociation (CID) with electrospray ionization mass spectroscopy (ESI–MS) to gain insights into the self-assembly process and structural information of amyloidogenic oligomers. We selected three tyrosine-containing sequences, NNQQNY, VQIVYK, and LYQLEN, which are known to form ordered β-sheet structures characteristic of amyloid fibrils, and another sequence, YGGFL, which is known to form isotropic structures. Y → A substituted sequences, NNQQNA, VQIVAK, and LAQLEN, were also investigated by CID-MS/MS. Our MS/MS analysis suggests that Y–Y interactions are important in dimer binding, and the charge state of the multiply charged oligomers is related to the formation of β-sheet.