Structural preferences of Aβ fragments in different micellar environments

Amyloid diseases occur due to conformational change in the native protein. Understanding the amyloid peptide structural stability and conformational preference at the molecular level in membranous environment may lead to advancement in drug design and therapy. The conformational preferences of amyloid peptide fragments, Aβ1–11, Aβ12–22, Aβ23–33 and Aβ34–42 was studied in buffers, trifluoroethanol (TFE) and sodium dodecyl sulfate (SDS) micelles using circular dichroism spectroscopy. The fragment, Aβ1–11 in TFE adopts a mixture of random coil and turn conformations. Aβ12–22 and Aβ23-33 underwent transition from random coil to helix conformation, while Aβ34–42 exhibited β-sheet conformation in initial stage which was unaltered on complete evaporation of TFE. Addition of SDS to Aβ12–22 and Aβ34–42 favors β-sheet structure, which was predominant in the case of Aβ34–42. However, in Aβ1–11 and Aβ23–33, no secondary structural change was noticed even at high SDS concentrations. On aging, all the peptide fragments showed β-sheet conformational transition. The C-terminal fragment has the ability to adopt predominant β-sheet conformation even in the presence of detergent and membrane mimicking environment. Altogether, the structural information gained from the short fragments could be further used for determining their role in the organization of Aβ peptide in stable fibril form.