One O-linked sugar can affect the coil-to-β structural transition of the prion peptide

摘要

It has been known that the structural transition from PrP~C to PrP~(Sc) leads to the prion formation. This putative conformational change challenges the central dogma of the protein folding theory―"one sequence, one structure." Generally, scientists believe that there must be either a posttranslational modification or environmental factors involved in this event However, all of the efforts to solve the mystery of the PrP~C to PrP~(Sc) transition have ended in vain so far. Here we provide evidence linking O-linked glycosylation to the structural transition based on prion peptide studies. We find that the O-linked α-GalNAc at Ser-135 suppresses the formation of amyloid fibril formation of the prion peptide at physiological salt concentrations, whereas the peptide with the same sugar at Ser-132 shows the opposite effect. Moreover, this effect is sugar specific. Replacing α-GalNAc with β-GlcNAc does not yield the same effect.