Fusogenic Alzheimer'S Peptide Fragment A Beta (29-42) In Interaction With Lipid Bilayers: Secondary Structure, Dynamics, And Specific Interaction With Phosphatidyl Ethanolamine Polar Heads As Revealed By Solid-State Nmr
The interaction of the native Alzheimer's peptide C‐terminal fragment Aβ (29–42), and two mutants (G33A and G37A) with neutral lipid bilayers made of POPC and POPE in a 9:1 molar ratio was investigated by solid‐state NMR. This fragment and the lipid composition were selected because they repres...
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Published in | Protein science Vol. 14; no. 5; pp. 1181 - 9 |
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Main Authors | , , , , , |
Format | Journal Article Web Resource |
Language | English |
Published |
Bristol
Cold Spring Harbor Laboratory Press
01.05.2005
Wiley-Blackwell |
Subjects | |
Online Access | Get full text |
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Summary: | The interaction of the native Alzheimer's peptide C‐terminal fragment Aβ (29–42), and two mutants (G33A and G37A) with neutral lipid bilayers made of POPC and POPE in a 9:1 molar ratio was investigated by solid‐state NMR. This fragment and the lipid composition were selected because they represent the minimum requirement for the fusogenic activity of the Alzheimer's peptide. The chemical shifts of alanine methyl isotropic carbon were determined by MAS NMR, and they clearly demonstrated that the major form of the peptide equilibrated in membrane is not in a helical conformation. 2H NMR, performed with acyl chain deuterated POPC, demonstrated that there is no perturbation of the acyl chain's dynamics and of the lipid phase transition temperature. 2H NMR, performed with alanine methyl‐deuterated peptide demonstrated that the peptide itself has a limited mobility below and above the lipid phase transition temperature (molecular order parameter equal to 0.94). MAS 31P NMR revealed a specific interaction with POPE polar head as seen by the enhancement of POPE phosphorus nuclei T2 relaxation. All these results are in favor of a β‐sheet oligomeric association of the peptide at the bilayer interface, preferentially recruiting phosphatidyl ethanolamine polar heads. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 scopus-id:2-s2.0-17744391390 Reprint requests to: Alain Milon, IPBS CNRS, 205 rte de Narbonne 31077 Toulouse, France; e-mail: alain.milon@ipbs.fr; fax: 33 5 61175424. |
ISSN: | 0961-8368 1469-896X 1469-896X |
DOI: | 10.1110/ps.041291405 |