PrP106-126 amide causes the semi-penetrated poration in the supported lipid bilayers.
A major hallmark of prion diseases is the cerebral amyloid accumulation of the pathogenic PrP(Sc), an abnormally misfolded, protease-resistant, and beta-sheet rich protein. PrP106-126 is the key domain responsible for the conformational conversion and aggregation of PrP. It shares important physicochemical characteristics with PrP(Sc) and presents similar neurotoxicity as PrP(Sc). By combination of fluorescence polarization, dye release assay and in situ time-lapse atomic force microscopy (AFM), we investigated the PrP106-126 amide interacting with the large unilamellar vesicles (LUVs) and the supported lipid bilayers (SLBs). The results suggest that the interactions involve a poration-mediated process: firstly, the peptide binding results in the formation of pores in the membranes, which penetrate only half of the membranes; subsequently, PrP106-126 amide undergoes the poration-mediated diffusion in the SLBs, represented by the formation and expansion of the flat high-rise domains (FHDs). The possible mechanisms of the interactions between PrP106-126 amide and lipid membranes are proposed based on our observations.
Zhong
Jian
J
Single-molecule and Nanobiology Laboratory, Department of Biophysics, School of Basic Medical Sciences and Biomed-X Center, Peking University, Beijing 100083, China.
Zheng
Wenfu
W
Huang
Lixin
L
Hong
Yuankai
Y
Wang
Lijun
L
Qiu
Yang
Y
Sha
Yinlin
Y
D000595:Amino Acid Sequence; D005454:Fluorescence Polarization; D008051:Lipid Bilayers / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D010539:Permeability; D011328:Prions / Q000378:metabolism*; D011487:Protein Conformation; D053835:Unilamellar Liposomes / Q000378:metabolism*
D008051:Lipid Bilayers; D010446:Peptide Fragments; D011328:Prions; D053835:Unilamellar Liposomes; C082632:prion protein (106-126)