Steric zippers, where the residues of two neighboring β-sheet layers are tightly interdigitated, have been proposed as fundamental structural units of amyloid fibrils by Eisenberg and co-workers. The steric zipper formed by polypeptides containing the palindromic sequence AGAAAAGA has a distinctive feature that the distance between two interdigitated β-sheet layers is comparable to the interstrand distance of the individual β-sheet. This structural motif is of great interest in the study of prion disease because the AGAAAAGA sequence is highly conserved in prion proteins of different species. In this work, the amyloid fibrils formed by the polypeptides of PrP(113-127), viz. Ac-AGAAAAGAVVGGLGG-NH(2), are taken as the model compound to investigate the biophysical principles governing the steric zipper formation. The target fibrils adopt the structural motif of class 7 steric zipper, which is formed by stacking of antiparallel β-sheet layers with residue 117 + k forming backbone hydrogen bonds to residue 120 - k. Implication of our results in the infectivity of scrapie prion is briefly discussed.
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