Interfacial properties of the M1 segment of the nicotinic acetylcholine receptor

Ernesto E. Ambroggio; Marcos A. Villarreal; Guillermo G. Montich; Dirk T.S. Rijkers; Maurits R.R. De Planque; Frances Separovic; Gerardo D. Fidelio

doi:10.1016/j.bpc.2005.12.007

Interfacial properties of the M1 segment of the nicotinic acetylcholine receptor

Ernesto E. Ambroggio, Marcos A. Villarreal, Guillermo G. Montich, Dirk T.S. Rijkers, Maurits R.R. De Planque, Frances Separovic, Gerardo D. Fidelio^*

^*Corresponding author for this work

Chemical Biology and Drug Discovery

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

We have studied the thermodynamic, surface, and structural properties of αM1 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 Å²/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 CCl₄, 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.

Original language	English
Pages (from-to)	171-176
Number of pages	6
Journal	Biophysical Chemistry
Volume	121
Issue number	3
DOIs	https://doi.org/10.1016/j.bpc.2005.12.007
Publication status	Published - 1 Jun 2006

Funding

This work was supported by grants from CONICET, FONCYT (PICT 0609228), SECYT-UNC, and Agencia Córdoba Ciencia. G. D. F. and G. G. M. are members of the Career of Investigator. E. E. A. and M. A. V. are fellows from CONICET. M. R. R. de P. was supported by fellowship S81-683 of The Netherlands Organization for Scientific Research (NWO).

Keywords

Distorted helix
Fourier-transform infrared spectroscopy
Gibbs adsorption free energy
Molecular dynamics simulation
Nicotinic acetylcholine receptor
Peptide monolayer
Peptide secondary structure
Peptide-lipid interaction
Peptide-lipid mixed monolayers
Transmembrane αM1 peptide

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10.1016/j.bpc.2005.12.007

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title = "Interfacial properties of the M1 segment of the nicotinic acetylcholine receptor",

abstract = "We have studied the thermodynamic, surface, and structural properties of αM1 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 {\AA}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 CCl4, 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.",

keywords = "Distorted helix, Fourier-transform infrared spectroscopy, Gibbs adsorption free energy, Molecular dynamics simulation, Nicotinic acetylcholine receptor, Peptide monolayer, Peptide secondary structure, Peptide-lipid interaction, Peptide-lipid mixed monolayers, Transmembrane αM1 peptide",

author = "Ambroggio, \{Ernesto E.\} and Villarreal, \{Marcos A.\} and Montich, \{Guillermo G.\} and Rijkers, \{Dirk T.S.\} and \{De Planque\}, \{Maurits R.R.\} and Frances Separovic and Fidelio, \{Gerardo D.\}",

year = "2006",

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doi = "10.1016/j.bpc.2005.12.007",

language = "English",

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T1 - Interfacial properties of the M1 segment of the nicotinic acetylcholine receptor

AU - Ambroggio, Ernesto E.

AU - Villarreal, Marcos A.

AU - Montich, Guillermo G.

AU - Rijkers, Dirk T.S.

AU - De Planque, Maurits R.R.

AU - Separovic, Frances

AU - Fidelio, Gerardo D.

PY - 2006/6/1

Y1 - 2006/6/1

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AB - We have studied the thermodynamic, surface, and structural properties of αM1 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 Å2/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 CCl4, 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.

KW - Distorted helix

KW - Fourier-transform infrared spectroscopy

KW - Gibbs adsorption free energy

KW - Molecular dynamics simulation

KW - Nicotinic acetylcholine receptor

KW - Peptide monolayer

KW - Peptide secondary structure

KW - Peptide-lipid interaction

KW - Peptide-lipid mixed monolayers

KW - Transmembrane αM1 peptide

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SN - 0301-4622

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SP - 171

EP - 176

JO - Biophysical Chemistry

JF - Biophysical Chemistry

IS - 3

ER -

Interfacial properties of the M1 segment of the nicotinic acetylcholine receptor

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