Jeane-Pierre Vilardaga, Ph.D.
Assistant Professor in Medicine

email jvilardaga@partners.org, phone (617) 724-8493, fax (617) 726-5669

Specialized transmembrane proteins known as G protein-coupled receptors (GPCRs) serve as universal cell surface switches to transmit hormones, neurotransmitter and other extracellular chemical signals into cells. GPCRs are kept in an inactive state until the binding of a ligand 'agonist' switches them into an active state within milliseconds. The transition between the inactive and active states involves the release of at least two important molecular constraints, known as the "ionic lock" between charged residues at the cytosolic sides of the receptor and the "rotamer toggle switch" in helix 6. We are interested in using intramolecular and intermolecualr fluorescence energy transfer (FRET) to dissect the molecular mechanisms that convert binding of ligands to activation of GPCRs.

Refereneces:

Lohse MJ, Bünemann M, Hoffmann C, Vilardaga JP, NikolaevVO. Monitoring receptor signaling by intramolecular FRET. Curr Opin Pharmacol. 2007 Oct;7(5):547-53. Epub 2007 Oct 4. Review.

Dean T, Vilardaga JP, Potts JT Jr, Gardella TJ. Altered Selectivity of Parathyroid Hormone (PTH) and PTH-Related Protein (PTHrP) for Distinct Conformations of the PTH/ PTHrP Receptor. Mol Endocrinol. 2008 Jan;22(1):156-66. Epub 2007 Sep 13.

Rochais F, Vilardaga JP, Nikolaev VO, Bünemann M, Lohse MJ, Engelhardt S. Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol. J Clin Invest. 2007 Jan;117(1):229-35.

Vilardaga JP. Switching modes for G protein-coupled receptor activation. Nat Chem Biol. 2006 Aug;2(8):395-6.

Nikolaev VO, Hoffmann C, Bünemann M, Lohse MJ, Vilardaga JP. Molecular basis of partial agonism at the neurotransmitter alpha2A-adrenergic receptor and Gi-protein heterotrimer. J Biol Chem. 2006 Aug 25;281(34):24506-11. Epub 2006 Jun 20.

Vilardaga JP, Steinmeyer R, Harms GS, Lohse MJ. Molecular basis of inverse agonism in a G protein-coupled receptor. Nat Chem Biol. 2005 Jun;1(1):25-8. Epub 2005 May 24.