PrP106-126 peptide disrupts lipid membranes: influence of C-terminal amidation.
PrP106-126 is located within the important domain concerning membrane related conformational conversion of human Prion protein (from cellular isoform PrP(C) to scrapie isoform PrP(Sc)). Recent advances reveal that the pathological and physicochemical properties of PrP106-126 peptide are very sensitive to its N-terminal amidation, however, the detailed mechanism remains unclear. In this work, we studied the interactions of the PrP106-126 isoforms (PrP106-126(CONH2) and PrP106-126(COOH)) with the neutral lipid bilayers by atomic force microscopy, surface plasmon resonance and fluorescence spectroscopy. The membrane structures were disturbed by the two isoforms in a similarly stepwise process. The distinct morphological changes of the membrane were characterized by formation of semi-penetrated defects and sigmoidal growth of flat high-rise domains on the supported lipid bilayers. However, PrP106-126(COOH) displayed a higher peptide-lipid binding affinity than PrP106-126(CONH2) (approximately 2.9 times) and facilitated the peptide-lipid interactions by shortening the lag time. These results indicate that the C-terminal amidation may influence the pathological actions of PrP106-126 by lowering the interaction potentials with lipid membranes.
Zheng
Wenfu
W
Single-molecule and Nanobiology Laboratory, Department of Biophysics, School of Basic Medical Sciences and Biomed-X Center, Peking University, Xueyuan Road No. 38, Beijing 100191, China.
Wang
Lijun
L
Hong
Yuankai
Y
Sha
Yinlin
Y
D000577:Amides / Q000737:chemistry*; D000595:Amino Acid Sequence; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008560:Membrane Fluidity; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry
D000577:Amides; D008051:Lipid Bilayers; D010446:Peptide Fragments; D011328:Prions; D020033:Protein Isoforms; C082632:prion protein (106-126)