Enhanced correction methods for hydrogen exchange-mass spectrometric studies of amyloid fibrils

We describe methods for minimization of and correction for artifactual forward and backward exchange occurring during hydrogen exchange-mass spectrometric (HX-MS) studies of amyloid fibrils of the Abeta(1-40) peptide. The quality of the corrected data obtained using published and new correction algorithms is evaluated quantitatively. Using the new correction methods, we have determined that 20.1 +/- 1.4 of the 39 backbone amide hydrogens in Abeta(1-40) exchange with deuteriums in 100 h when amyloid fibrils of this peptide are suspended in D(2)O. These data reinforce our previous conclusions based on uncorrected data that amyloid fibrils contain a rigid protective core structure that involves only about half of the Abeta backbone amides. The methods developed here should be of general value for HX-MS studies of amyloid fibrils and other protein aggregates.