Structural variations in the cross-beta core of amyloid beta fibrils revealed by deep UV resonance Raman spectroscopy.

Understanding fibrillogenesis at a molecular level requires detailed structural characterization of amyloid fibrils. The combination of deep UV resonance Raman (DUVRR) spectroscopy and post mortem hydrogen-deuterium exchange (HX) was utilized for probing parallel vs antiparallel beta-sheets in fibrils prepared from full-length Abeta(1-40) and Abeta(34-42) peptides， respectively. Using previously published structural data based on solid-state NMR analysis， we verified the applicability of Asher's approach for the quantitative characterization of peptide conformation in the Abeta(1-40) fibril core. We found that the conformation of the parallel beta-sheet in the Abeta(1-40) fibril core is atypical for globular proteins， while in contrast， the antiparallel beta-sheet in Abeta(32-42) fibrils is a common structure in globular proteins. In contrast to the case for globular proteins， the conformations of parallel and antiparallel beta-sheets in Abeta fibril cores are substantially different， and their differences can be distinguished by DUVRR spectroscopy.