Parent Category: Laboratoires Published: Monday, 27 June 2016

Pharmacology and Structural Biology of Membrane Proteins

 

Granier

 Sébastien GRANIER

 

 IGF - UMR 5203/U 661

 141, rue de la Cardonille, 34396 Montpellier

 

Phone: +33 4 34 35 92 80

Email: sebastien.granier@igf.cnrs.fr

 

 

Website

 

 

 

The Granier Lab aims at characterizing the molecular and structural mechanisms of GPCRs and PAQRs function. GPCRs and PAQRs present a seven transmembrane domain (7TM) which acts as a receptor and a transducer of extracellular signals within the cell to regulate a wide variety of physiological function.As such, they are the subject of intense studies both in academic labs and in industry with important drug discovery programs. Despite recents advance in the field, there is still an important lack of knowledge of 7TM signalling mechanisms and pharmacology. This is mainly due to the challenges associated with the characterization of membrane protein structure and function.

To fill this gap of knowledge, we are developing an innovative integrated strategy combining state-of-the-art molecular and structural pharmacology approaches including:

 

1) Molecular analyses of transmembrane signalling network using resonance energy transfer measurement in living cells and proteomic analyses
and
2) Structural analyses of receptors and signalling complexes using biochemistry, fluorescence, NMR spectroscopy and X-ray crystallography.

 

 

Keywords: opioids, adiponectin, receptor activation, pain, obesity-related diseases

 

 

Main publications

  • Structural insights into adiponectin receptors suggest ceramidase activity.
    Vasiliauskaité-Brooks I, Sounier R, Rochaix P, Bellot G, Fortier M, Hoh F, De Colibus L, Bechara C, Saied EM, Arenz C, Leyrat C, Granier S. Nature. 2017 Apr 06;544:120-123. doi: 10.1038/nature21714.
  • Structural insights into μ-opioid receptor activation.
    Huang W, Manglik A, Venkatakrishnan AJ, Laeremans T, Feinberg EN, Sanborn AL, Kato HE, Livingston KE, Thorsen TS, Kling RC, Granier S, Gmeiner P, Husbands SM, Traynor JR, Weis WI, Steyaert J, Dror RO, Kobilka BK. Nature. 2015 Aug 20;524(7565):315-21.
  • Propagation of conformational changes during μ-opioid receptor activation.
    Sounier R, Mas C, Steyaert J, Laeremans T, Manglik A, Huang W, Kobilka BK, Déméné H, Granier S. Nature. 2015 Aug 20;524(7565):375-8.
  • Structure of the δ-opioid receptor bound to naltrindole.
    Granier S, Manglik A, Kruse AC, Kobilka TS, Thian FS, Weis WI, Kobilka BK. Nature. 2012 May 16;485(7398):400-4.
  • Structural insights into biased G protein-coupled receptor signaling revealed by fluorescence spectroscopy.
    Rahmeh R, Damian M, Cottet M, Orcel H, Mendre C, Durroux T, Sharma KS, Durand G, Pucci B, Trinquet E, Zwier JM, Deupi X, Bron P, Banères
    JL, Mouillac B, Granier S. Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6733-8.
  • Crystal structure of the μ-opioid receptor bound to a morphinan antagonist.
    Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, Pardo L, Weis WI, Kobilka BK, Granier S. Nature. 2012 Mar 21;485(7398):321-6.
  • Distinct roles of metabotropic glutamate receptor dimerization in agonist activation and G-protein coupling.
    El Moustaine D.*, Granier S.*#, Doumazane E., Scholler P., Rahmeh R., Bron P., Mouillac B., Banères J.L., Rondard P., and Pin, J.P#. Distinct roles of metabotropic glutamate receptor dimerization in agonist activation and G-protein coupling. Proc Natl Acad Sci U S A 2012 Oct 2;109(40):16342-7. *these authors contributed equally to this work. # Co-corresponding authors.
  • A new era of GPCR structural and chemical biology.
    Granier S, and Kobilka B.K. Nat. Chem. Biol. 2012 Jul 18;8(8):670-3.
  • Counting low-copy number proteins in a single cell.
    Huang B, Wu H, Bhaya D, Grossman A, Granier S, Kobilka BK, Zare RN. Science. 2007 Jan 5;315(5808):81-4.
  • Structure and conformational changes in the C-terminal domain of the beta2-adrenoceptor: insights from fluorescence resonance energy transfer studies.
    Granier S, Kim S, Shafer AM, Ratnala VR, Fung JJ, Zare RN, Kobilka B. J Biol Chem. 2007 May 4;282(18):13895-905.

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