Effect of the lipidic membrane composition on the dynamical properties of the µ opioid receptor

Research output: Contribution to conferencePoster

Abstract

Lipid rafts drifting in the membrane as an
island in the ocean. Such structure, rigid and
thick, due to the large amount of cholesterol
(30%) and sphingolipids, remains
controversial because of its difficult
experimental characterization [1]. Lipid rafts
protect the protein of phosphatases present in
the membrane and increase the efficiency of
signaling pathways. The protein/lipid
interactions modulate the protein
conformation, which condition their entry into
lipid rafts.
Opioid receptors, whose structures were revealed in 2012, are part of the G-protein coupled receptor
(GPCRs), target of 50 % of drugs on the market today [2]. The structural and functional properties of
transmembrane proteins are affected by the lipid environment [3]. The hydrophobic mismatch promotes
dimerization by reducing the entropy due to the adaptation of the membrane to protein [4].
Dimerization of μ protein involves different signaling pathways but are still poorly understood, as well
as the presence of dimers in lipid rafts [5].
To understand these processes, molecular dynamics (MD) simulations can provide numerous
clarifications, from very detailed (all-atoms) to lower resolutions (coarse-grained). Ultimately, our goal
is to perform MD simulations with the most realistic lipid composition, the simplest and most
significant in terms of protein/lipid interactions, in order to guide the docking experiments and show
the importance of the interaction of a protein with a lipid towards its structural and functional
properties.
Bibliography:
[1] Quinn P. J. (2010) A lipid matrix model of membrane raft structure Progress in Lipid Research 49:
390-406
[2] Manglik A., Kruse A., Kobilka T., Thian F., Mathiesen J., Sunahara R., Pardo L., Weis W.,
Kobilka B., Granier S. (2012) Crystal structure of the mu-opioid receptor bound to a morphinan
antagonist Nature 485: 321-7
[3] Jastrzebska B., Debinski A., Filipek S., Palczewski K. (2011) Role of membrane integrity on G
protein-coupled receptors: rhodopsin stability and function Progress in Lipid Research 50: 267-77
[4] Soubias O., Niu S.-L., Mitchell D., Gawrisch K. (2008) Lipid-rhodopsin hydrophobic mismatch
alters rhodopsin helical content Journal of American Chemistry Society 130: 12465-71
[5] Borroto-Escuela D., Romero-Fernandez W., Rivera A., Van Craenenbroeck K., Tarakanov A.,
Agnati L., Fuxe K. (2013) On the G-protein-coupled receptor heteromers and their allosteric receptorreceptor
interactions in the central nervous system: focus on their role in pain modulation
Evidence-Based Complementary and Alternative Medicine 17: 563716-33
Original languageEnglish
Publication statusPublished - 4 Apr 2014
EventCECAM workshop How proteins can shape and sense membranes--a closer look at hybrid models - Freie Universität Berlin, Institute of Mathematics, Berlin, Germany
Duration: 2 Apr 20144 Apr 2014

Conference

ConferenceCECAM workshop How proteins can shape and sense membranes--a closer look at hybrid models
CountryGermany
CityBerlin
Period2/04/144/04/14

Projects

Equipment

  • Activities

    • 1 Participation to a Symposium, a study Day

    CECAM workshop How proteins can shape and sense membranes--a closer look at hybrid models

    Marie-Ange Angladon (Poster)

    2 Apr 20144 Apr 2014

    Activity: Participating in or organising an event typesParticipation to a Symposium, a study Day

    Cite this

    Angladon, M-A., Fossepre, M., Leherte, L., & Vercauteren, D. (2014). Effect of the lipidic membrane composition on the dynamical properties of the µ opioid receptor. Poster session presented at CECAM workshop How proteins can shape and sense membranes--a closer look at hybrid models, Berlin, Germany.