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  4. Effect of the Synaptic Plasma Membrane on the Stability of the Amyloid Precursor Protein Homodimer
 
research article

Effect of the Synaptic Plasma Membrane on the Stability of the Amyloid Precursor Protein Homodimer

Audagnotto, Martina  
•
Lemmin, Thomas  
•
Barducci, Alessandro
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2016
The Journal of Physical Chemistry Letters

The proteolytic cleavage of the transmembrane (TM) domain of the amyloid precursor protein (APP) releases amyloid-beta (A beta) peptides, which accumulation in the brain tissue is an early indicator of Alzheimer's disease. We used multiscale molecular dynamics simulations to investigate the stability of APP-TM dimer in realistic models of the synaptic plasma membrane (SPM). Between the two possible dimerization motifs proposed by NMR and EPR, namely G(709)XXXA(713) and G(700)XXXG(704)XXXG(708), our study revealed that the dimer promoted by the G(709)XXXA(713) motif is not stable in the SPM due to the competition with highly unsaturated lipids that constitute the SPM. Under the same conditions, the dimer promoted by the G(700)XXXG(704)XXXG(708) motif is instead the most stable species and likely the most biologically relevant. Independently of the dimerization state, both these motifs can be involved in the recruitment of cholesterol molecules.

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Type
research article
DOI
10.1021/acs.jpclett.6b01721
Web of Science ID

WOS:000383641800007

Author(s)
Audagnotto, Martina  
Lemmin, Thomas  
Barducci, Alessandro
Dal Peraro, Matteo  
Date Issued

2016

Publisher

Amer Chemical Soc

Published in
The Journal of Physical Chemistry Letters
Volume

7

Issue

18

Start page

3572

End page

3578

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPDALPE  
Available on Infoscience
October 18, 2016
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/130204
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