Abstract
The spatial structure of Alzheimer’s amyloid Aβ10–35-NH2 peptide in aqueous solution at pH 7.3 and in SDS micelles was investigated by use of a combination of the residual dipolar coupling method and two-dimensional NMR spectroscopy (TOCSY, NOESY). At pH 7.3 Aβ10–35-NH2 adopts a compact random-coil conformation whereas in SDS micellar solutions two helical regions (residues 13–23 and 30–35) of Aβ10–35-NH2 were observed. By use of experimental data, the structure of “peptide–micelle” complex was determined; it was found that Aβ10–35-NH2 peptide binds to the micelle surface at two regions (residues 17–20 and 29–35).
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Abbreviations
- AD:
-
Alzheimer’s disease
- APP:
-
Amyloid precursor protein
- CMC:
-
Critical micelle concentration
- DHPG:
-
Dihexanoylphosphatidylglycerol
- Fmoc:
-
9-Fluorenylmethyloxycarbonyl groups
- HBTU:
-
O-Benzotriazole-N,N,N′,N′-tetramethyluronium hexafluorophosphate
- HSQC:
-
Heteronuclear single-quantum coherence spectroscopy
- HMBC:
-
Heteronuclear multiple bond correlation
- NMR:
-
Nuclear magnetic resonance
- NOESY:
-
Nuclear Overhauser effect spectroscopy
- SDS:
-
Sodium dodecyl sulfate
- TOCSY:
-
Total correlation spectroscopy
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Acknowledgments
The work was supported by the Ministry of Education and Science of the Republic of Tatarstan (project no. 13-03-97041) and by the Ministry of Education and Science of the Russian Federation (KFU, code 2.2792.2011). A.V.F. and O.N.A. are grateful to the Foundation in memory of J.C. and Seth M. Kempe for grants, from which equipment for the peptide synthesis and purification was purchased. We also acknowledge Dr S. Afonin for electrospray mass spectrometric analysis of the peptide.
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Usachev, K.S., Filippov, A.V., Antzutkin, O.N. et al. Use of a combination of the RDC method and NOESY NMR spectroscopy to determine the structure of Alzheimer’s amyloid Aβ10–35 peptide in solution and in SDS micelles. Eur Biophys J 42, 803–810 (2013). https://doi.org/10.1007/s00249-013-0928-7
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DOI: https://doi.org/10.1007/s00249-013-0928-7