Effect of Familial Mutations on Salt-Bridge Formation in Aβ42 Monomers

Recent experimental and computational studies suggest that there is a U-shape motif in the middle region (20-30) of Aβ monomers that is stabilized by salt bridges between residues Glu22/Asp23 (as the anions) and Lys28 (as the cation). It seems that the competition between two anionic residues (D23 and E22) to make the salt-bridge with the Lys28, can be considered as a controlling parameter in yielding a Aβ42 monomer with the U-shaped conformation. Consequently, by replacing each of these anionic residues with neutral residues containing small side-chain (such as Gly, in E22G) the salt-bridges formation between residues Glu22/Asp23 and Lys28 is facilitated.