Insight into the Packing Pattern of β₂ Fibrils: A Model Study of Glutamic Acid Rich Oligomers with ¹³C Isotopic Edited Vibrational Spectroscopy

Abstract

Polyglutamic acid at low pH forms aggregates and self-assembles into a spiral, fibril-like superstructure formed as a β₂-type sheet conformation that has a more compact intersheet packing than commonly found. This is stabilized by three-centered bifurcated hydrogen bonding of the amide carbonyl involving the protonated glutamic acid side chain. We report vibrational spectroscopic results and analyses for oligopeptides rich in glutamic acid enhanced with ¹³C isotope labeling in a study modeling low pH poly-Glu self-assembly. Our results indicate bifurcated H-bonding and β₂ aggregation can be attained in these model decamers, confirming they have the same conformations as poly-Glu. We also prepared conventional β₁-sheet aggregates by rapid precipitation from the residual peptides in the higher pH supernatant. By comparing the isotope-enhanced IR and VCD spectra with theoretical predictions, we deduced that the oligo-Glu β₂ structure is based on stacked, twisted, antiparallel β-sheets. The best fit to theoretical predictions was obtained for the strands being out of register, sequentially stepped by one residue, in a ladder-like fashion. The alternate β₁ conformer for this oligopeptide was similarly shown to be antiparallel but was less ordered and apparently had a different registry in its aggregate structure