Dynamics and cleavability of the alpha-cleavage site of APP(684-726) in different lipid environments
Marenchino, Marco, Williamson, Phillip T.F., Murri, Samuel, Zandomeneghi, Giorgia, Wunderli-Allenspach, Heidi, Meier, Beat H. and Kramer, Stefanie D. (2008) Dynamics and cleavability of the alpha-cleavage site of APP(684-726) in different lipid environments. Biophysical Journal, 95, (3), 1460-1473. (doi:10.1529/biophysj.108.129726). (PMID:18390599).
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Description/Abstract
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 2H-Ala713, 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 Tc. The residue 15N-Ala692, which is in the vicinity of the α-cleavage site, i.e., Lys687, showed less motion after reconstitution in distearoyl-phosphatidylcholine liposomes <Tc than in PhC, DMPC, or sphingomyelin vesicles. In all tested liposomal systems the α-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 α-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
| Item Type: | Article |
|---|---|
| ISSNs: | 0006-3495 (print) |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| Divisions: | University Structure - Pre August 2011 > School of Biological Sciences |
| Item ID: | 72080 |
| Date Deposited: | 20 Jan 2010 |
| Last Modified: | 09 Jun 2011 14:31 |
| Contributors: | Marenchino, Marco (Author) Williamson, Phillip T.F. (Author) Murri, Samuel (Author) Zandomeneghi, Giorgia (Author) Wunderli-Allenspach, Heidi (Author) Meier, Beat H. (Author) Kramer, Stefanie D. (Author) |
| Date: | August 2008 |
| Status: | Published |
| Contact Email Address: | P.T.Williamson@soton.ac.uk |
| URI: | http://eprints.soton.ac.uk/id/eprint/72080 |
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