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.
Bioorganic Chemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600020, India.
Dhandayuthapani
D
Sambasivam
Senthilkumar
S
Sivanesan
Ben S
BS
Ashok
Jayakumar
J
Rajadas
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D002942:Circular Dichroism; D006801:Humans; D008823:Micelles; D010446:Peptide Fragments / Q000737:chemistry / Q000648:ultrastructure; D017433:Protein Structure, Secondary; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D013997:Time Factors; D014270:Trifluoroethanol / Q000737:chemistry
D000682:Amyloid; D016229:Amyloid beta-Peptides; D008823:Micelles; D010446:Peptide Fragments; D012996:Solutions; D012967:Sodium Dodecyl Sulfate; D014270:Trifluoroethanol