Probing the secondary structure of A[beta] (1-40) fibrils

Limited information has been obtained on the secondary structure of amyloid fibrils. In the absence of high resolution structural data, several groups have proposed models for amyloid fibril structure. However,these models differ in hydrogen bonding patterns and residues that make up the rigid core of the fibril structure. Significant insight into fibril structure could be derived form a knowledge of the hydrogen bonding patterns within fibrils. Structural studies were performed on Aβ (1-40) fibrils using hydrogen exchange mass spectrometry as well as limited proteolysis under native conditions. Data was obtained which illustrate differential amounts of exchange within the monomer sequence. Results also suggest peptide bond exposure at specific residues within the N-terminal portion of Aβ incorporated into fibrils.