The alphaM1 segment of the nicotinic acetylcholine receptor exhibits conformational flexibility in a membrance environment
de Planque, M R R, Rijkers, D T S, Fletcher, J I, Liskamp, R M J and Separovic, F (2004) The alphaM1 segment of the nicotinic acetylcholine receptor exhibits conformational flexibility in a membrance environment. Biochimica et Biophysica Acta, 1665, (1-2), 40-47.
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The transmembrane domain of the nicotinic acetylcholine receptor (nAChR) is predominantly α-helical, and of the four distinctly different transmembrane M-segments, only the helicity of M1 is ambiguous. In this study, we have investigated the conformation of a membrane-embedded synthetic M1 segment by solid-state nuclear magnetic resonance (NMR) methods. A 35-residue peptide representing the extended αM1 domain 206–240 of the Torpedo californica nAChR was synthesized with specific 13C- and 15N-labelled amino acids, and was incorporated in different phosphatidylcholine model membranes. The chemical shift of the isotopic labels was resolved by magic angle spinning (MAS) NMR and could be related to the secondary structure of the αM1 analog at the labelled sites. Our results show that the membrane-embedded αM1 segment forms an unstable α-helix, particularly near residue Leu18 (αLeu223 in the entire nAChR). This non-helical tendency was most pronounced when the peptide was incorporated in fully hydrated phospholipid bilayers, with an estimated 40–50% of the peptides having an extended conformation at position Leu18. We propose that the conserved proline residue at position 16 in the αM1 analog imparts a conformational flexibility on the M1 segments that could enable membrane-mediated modulation of nAChR activity.
|Keywords:||Nicotinic acetylcholine receptor, alphaMI transmembrane segment, Conformation, Phosphatidylcholine model membranes, Solid-state NMR|
|Divisions:||Faculty of Physical and Applied Science > Electronics and Computer Science > NANO
|Date Deposited:||16 Oct 2007|
|Last Modified:||02 Mar 2012 12:41|
|Contributors:||de Planque, M R R (Author)
Rijkers, D T S (Author)
Fletcher, J I (Author)
Liskamp, R M J (Author)
Separovic, F (Author)
|Further Information:||Google Scholar|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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