Interaction of Alzheimer beta-amyloid peptide(1-40) with lipid membranes.
The beta-amyloid peptide beta AP(1-40), a 40-amino acid residues peptide, is one of the major components of Alzheimer's amyloid deposits. beta AP(1-40) exhibits only a limited solubility in aqueous solution and undergoes a concentration-dependent, cooperative random coil reversible beta-structure transition for Cpep > 10 microM [Terzi, E., Hölzemann, G., and Seelig, J. (1995) J. Mol. Biol. 252, 633-642]. In the presence of acidic lipid, the equilibrium is shifted further toward beta-structured aggregates. We have now characterized the lipid-peptide interaction using circular dichroism (CD) spectroscopy, lipid monolayers, and deuterium and phosphorus-31 solid-state nuclear magnetic resonance (NMR). CD spectroscopy revealed a distinct interaction between beta AP(1-40) and negatively charged unilamellar vesicles. In addition to the random coil reversible beta-structured aggregate equilibrium at low lipid-to-peptide (L/P) ratios, a beta-structure -->alpha-helix transition was observed at L/P > 55. beta AP(1-40) was found to insert into acidic monolayers provided the lateral pressure was low (20 mN/m). The extent of incorporation increased distinctly with the content of acidic lipid in the monolayer. However, at a lipid packing density equivalent to that of a bilayer (lateral pressure > or = 32 mN/m), no insertion of beta AP(1-40) was observed. The lipid molecular structure in the presence of beta AP(1-40) was studied with NMR. Phosphatidylcholine (PC) was selectively deuterated at the choline headgroup and at the cis-double bond of the oleic acyl chain and mixed with phosphatidylglycerol (PG). Phosphorus-31 NMR showed that the lipid phase retained the bilayer structure at all lipid-to-protein ratios. Deuterium NMR revealed no change in the headgroup conformation of the choline moiety or in the flexibility and ordering of the hydrocarbon chains upon the addition of beta AP-(1-40). It can be concluded that beta AP(1-40) binds electrostatically to the outer envelope of the polar headgroup region without penetrating between the polar groups. The data suggest a new mechanism of helix formation induced by the proper alignment of five positive charges of beta AP(1-40) on the negatively charged membrane template.
Terzi
E
E
Department of Biophysical Chemistry, University of Basel, Switzerland.
Hölzemann
G
G
Seelig
J
J
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D002942:Circular Dichroism; D003903:Deuterium; D008567:Membranes, Artificial; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000378:metabolism*; D010759:Phosphorus Isotopes; D011485:Protein Binding; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D008567:Membranes, Artificial; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010759:Phosphorus Isotopes; C078592:amyloid beta-protein (1-40); C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; D003903:Deuterium; C028694:1-palmitoyl-2-oleoylphosphatidylcholine