Effects of lipid composition and phase on the membrane interaction of the prion peptide 106-126 amide.
Lipid rafts are specialized liquid-ordered (L(o)) phases of the cell membrane that are enriched in sphingolipids and cholesterol (Chl), and surrounded by a liquid-disordered (L(d)) phase enriched in glycerophospholipids. Lipid rafts are involved in the generation of pathological forms of proteins that are associated with neurodegenerative diseases. To investigate the effects of lipid composition and phase on the generation of pathological forms of proteins, we constructed an L(d)-gel phase-separated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/sphingomyelin (from bovine brain (BSM))-supported lipid bilayer (SLB) and an L(d)-L(o) phase-separated POPC/BSM/Chl SLB. We used in situ time-lapse atomic force microscopy to study the interactions between these SLBs and the prion peptide K(106)TNMKHMAGAAAAGAVVGGLG(126) (PrP106-126) amide, numbered according to the human prion-peptide sequence. Our results show that: 1), with the presence of BSM in the L(d) phase, the PrP106-126 amide induces fully penetrated porations in the L(d) phase of POPC/BSM SLB and POPC/BSM/Chl SLB; 2), with the presence of both BSM and Chl in the L(d) phase, the PrP106-126 amide induces the disintegration of the L(d) phase of POPC/BSM/Chl SLB; and 3), with the presence of both BSM and Chl in the L(o) phase, PrP106-126 amide induces membrane thinning in the L(o) phase of POPC/BSM/Chl SLB. These results provide comprehensive insight into the process by which the PrP106-126 amide interacts with lipid membranes.
Zhong
Jian
J
Single-Molecule and Nanobiology Laboratory, Department of Biophysics, School of Basic Medical Sciences, Biomed-X Center, and Center for Protein Science, Peking University, Beijing 100083, China.
Yang
Chunhui
C
Zheng
Wenfu
W
Huang
Lixin
L
Hong
Yuankai
Y
Wang
Lijun
L
Sha
Yinlin
Y
D002463:Cell Membrane Permeability; D002942:Circular Dichroism; D003902:Detergents / Q000737:chemistry; D016014:Linear Models; D008051:Lipid Bilayers / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008956:Models, Chemical; D017830:Octoxynol / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D010539:Permeability; D044367:Phase Transition; D010713:Phosphatidylcholines / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D013109:Sphingomyelins / Q000737:chemistry*
D003902:Detergents; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D011328:Prions; D013109:Sphingomyelins; C082632:prion protein (106-126); D017830:Octoxynol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine