Interfacial properties of the M1 segment of the nicotinic acetylcholine receptor.
We have studied the thermodynamic, surface, and structural properties of alphaM1 transmembrane sequence of the nicotinic acetylcholine receptor (nAChR) by using Langmuir monolayer, FT-IR spectroscopy and molecular dynamics simulation techniques in membrane-mimicking environments. M1 spontaneously incorporates into a lipid-free air-water interface, showing a favourable adsorption free energy of -7.2 kcal/mol. A cross-sectional molecular area of 210 A(2)/molecule, a surface potential of 4.2 fV/molecule and a high stability of the film were deducted from pure M1 monolayers. FT-IR experiments and molecular dynamics simulations in membrane-mimicking environments (sodium-dodecyl-sulfate and CCl(4), respectively) indicate coexistence between helical and non-helical structures. Furthermore, mixed peptide-lipid monolayers and monolayer penetration experiments were performed in order to study the peptide-lipid interaction. Mixed with condensed lipids (dipalmitoyl-phosphocholine, and dipalmitoyl-phosphoglycerol), M1 shows immiscible/miscible behaviour at low/high peptide concentration, respectively. Conversely, a complete miscible peptide-lipid interface is observed with liquid-expanded lipids (palmitoyl-oleoyl-phosphocholine, and palmitoyl-oleoyl-phosphoglycerol). Peptide penetration experiments demonstrate that the M1 peptide preferentially interacts with zwitterionic phosphocholine interfaces.
CIQUIBIC-CONICET, Departamento de Química Biológica, Facultad de Ciencias Químicas, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba, Argentina, (CP X5000HUA).
Ernesto E
EE
Ambroggio
Marcos A
MA
Villarreal
Guillermo G
GG
Montich
Dirk T S
DT
Rijkers
Maurits R R
MR
De Planque
Frances
F
Separovic
Gerardo D
GD
Fidelio
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000327:Adsorption; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry; D003198:Computer Simulation; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D008823:Micelles; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D014867:Water; D015060:1,2-Dipalmitoylphosphatidylcholine; D012967:Sodium Dodecyl Sulfate; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine