Spectroscopic evidence for the existence of an obligate pre-fibrillar oligomer during glucagon fibrillation.
The 29-residue peptide hormone glucagon has been used as a model system for the study of amyloid-like fibrils. Atomic force microscopy (AFM) studies have detected putative oligomeric species during this lag phase, but this has not been confirmed by any spectroscopic technique. Here we use an attached pyrene group to detect association (excimer formation) between individual glucagon molecules. Our data show that excimer formation precedes fibrillation both at different pHs and with sulfate, and support our original proposal that glucagon fibril formation is preceded by oligomer formation. We suggest that pyrene-labelling may be a useful way to monitor oligomer formation during protein fibrillation.
Christensen
Peter Astrup
PA
Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK - 8000 Aarhus C, Denmark.
Pedersen
Jesper Søndergaard
JS
Christiansen
Gunna
G
Otzen
Daniel Erik
DE
D001704:Biopolymers / Q000737:chemistry*; D005934:Glucagon / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D013050:Spectrometry, Fluorescence
D001704:Biopolymers; D005934:Glucagon