Biophysical Studies Of The Membrane Interactions Of A Transthyretin Fragment TTR(10-20)

Abstract

TTR(10-20) is a peptide derived from transthyretin, a 127 amino acid amyloid protein. Previous studies on TTR(10-20) have shown that this peptide could form protofibrils and fibrils in vitro. These are very rich β-sheet structures, insoluble at physiological pH. In vivo, protofibrils and fibrils deposit on tissues and lead to degenerescence. The goal of the present study is to characterize peptide structure and membrane interactions using different spectroscopic techniques.The secondary structure of TTR(10-20) was determined by Fourier transform infrared (FTIR) spectroscopy. More specifically, the information about the peptide secondary structure is given by the amide I band, which was monitored as a function of temperature and lipid composition of the bilayer. On most spectra, there is an aborption band around 1620 cm−1, corresponding to an intermolecular β-sheet structure such as protofibrils and fibrils. The area of this band increases with increasing temperature while the band corresponding to disordered structures decreases. The nature of the lipid head group also appears to have an impact on the aggregation of TTR(10-20).The lipid bilayer is also affected by the presence and the proportion of peptide. Solid-state 31P and 2H nuclear magnetic resonance spectroscopy were used in the present study to determine the location of the peptide in the bilayer. More specifically, 31P NMR is used to investigate the effect of TTR(10-20) on the lipid head group while 2H NMR is used to investigate the effect of the peptide on the lipid acyl chains.