Membrane destabilization induced by beta-amyloid peptide 29-42: importance of the amino-terminus.
Increasing evidence implicates interactions between Abeta-peptides and membrane lipids in Alzheimer's disease. To gain insight into the potential role of the free amino group of the N-terminus of Abeta29-42 fragment in these processes, we have investigated the ability of Abeta29-42 unprotected and Abeta29-42 N-protected to interact with negatively-charged liposomes and have calculated the interaction with membrane lipids by conformational analysis. Using vesicles mimicking the composition of neuronal membranes, we show that both peptides have a similar capacity to induce membrane fusion and permeabilization. The fusogenic effect is related to the appearance of non-bilayer structures where isotropic motions occur as shown by 31P and 2H NMR studies. The molecular modeling calculations confirm the experimental observations and suggest that lipid destabilization could be due to the ability of both peptides to adopt metastable positions in the presence of lipids. In conclusion, the presence of a free or protected (acetylated) amino group in the N-terminus of Abeta29-42 is therefore probably not crucial for destabilizing properties of the C-terminal fragment of Abeta peptides.
Mingeot-Leclercq
Marie Paule
MP
Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, Avenue E. Mounier 73, Bt 7370, B-1200, Brussels, Belgium. mingeot@facm.ucl.ac.be
Lins
Laurence
L
Bensliman
Mariam
M
Van Bambeke
Françoise
F
Van Der Smissen
Patrick
P
Peuvot
Jacques
J
Schanck
André
A
Brasseur
Robert
R
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry; D002463:Cell Membrane Permeability / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry*; D008561:Membrane Fusion / Q000187:drug effects; D008958:Models, Molecular; D009474:Neurons / Q000648:ultrastructure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000494:pharmacology*; D013696:Temperature
D016229:Amyloid beta-Peptides; D008081:Liposomes; D010446:Peptide Fragments