Structural preferences of AI super(2) fragments in different micellar environments

• Published in: Neuropeptides (Edinburgh) Vol. 45; no. 6; pp. 369 - 376
• Main Authors: Sambasivam, Dhandayuthapani, Sivanesan, Senthilkumar, Ashok, Ben S, Rajadas, Jayakumar
• Format: Journal Article
• Language: English
• Published: 01.12.2011
• ISSN: 0143-4179
• DOI: 10.1016/j.npep.2011.09.001

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, AI super(2) sub(1-11), AI super(2) sub(12-22), AI super(2) sub(23-33) and AI super(2) sub(34-42) was studied in buffers, trifluoroethanol (TFE) and sodium dodecyl sulfate (SDS) micelles using circular dichroism spectroscopy. The fragment, AI super(2) sub(1-11) in TFE adopts a mixture of random coil and turn conformations. AI super(2) sub(12-22) and AI super(2) sub(23-33) underwent transition from random coil to helix conformation, while AI super(2) sub(34-42) exhibited I super(2)-sheet conformation in initial stage which was unaltered on complete evaporation of TFE. Addition of SDS to AI super(2) sub(12-22) and AI super(2) sub(34-42) favors I super(2)-sheet structure, which was predominant in the case of AI super(2) sub(34-42). However, in AI super(2) sub(1-11) and AI super(2) sub(23-33), no secondary structural change was noticed even at high SDS concentrations. On aging, all the peptide fragments showed I super(2)-sheet conformational transition. The C-terminal fragment has the ability to adopt predominant I super(2)-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 AI super(2) peptide in stable fibril form.