Dynamics and Cleavability at the α-Cleavage Site of APP(684-726) in Different Lipid Environments
| Autor: | Giorgia Zandomeneghi, Heidi Wunderli-Allenspach, Stefanie D. Krämer, Marco Marenchino, Phillip T.F. Williamson, Samuel Murri, Beat H. Meier |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Liposome Binding Sites biology Vesicle Membrane lipids technology industry and agriculture Biophysics Amyloid beta-Protein Precursor Membrane Lipids chemistry.chemical_compound Transmembrane domain Models Chemical chemistry Biochemistry Cell Biophysics Phosphatidylcholine Liposomes Amyloid precursor protein biology.protein Computer Simulation lipids (amino acids peptides and proteins) Sphingomyelin Peptide sequence Protein Binding |
| Zdroj: | Biophysical Journal. 95:1460-1473 |
| ISSN: | 0006-3495 |
| Popis: | The occurrence of late-onset Alzheimer's disease has been related to the lipid homeostasis. We tested whether the membrane lipid environment affects the dynamics and cleavability of a model peptide corresponding to the amino acid sequence 684-726 of the amyloid precursor protein APP reconstituted in liposomes. Solid-state NMR with (2)H-Ala(713), which is located within the putative transmembrane domain, suggested that the peptide observes less rotational motion in egg phosphatidylcholine (PhC) membranes than in dimyristoyl-phosphatidylcholine (DMPC) bilayers above the main phase transition temperature T(c). The residue (15)N-Ala(692), which is in the vicinity of the alpha-cleavage site, i.e., Lys(687), showed less motion after reconstitution in distearoyl-phosphatidylcholine liposomesT(c) than in PhC, DMPC, or sphingomyelin vesicles. In all tested liposomal systems the alpha-cleavage site was accessible for hydrolysis by trypsin. However, the catalytic rate constant was higher in the PhC and DMPC than in the sphingomyelin and distearoyl-phosphatidylcholine systems. In conclusion, the dynamics of APP(684-726) on the transmembrane level as well as the motion of the alpha-cleavage site and its hydrolysis by a model enzyme are dependent on the bilayer characteristics. This could be relevant for the processing of APP in vivo. |
| Databáze: | OpenAIRE |
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