1. Structural Insights into the Dynamic Process of β2-Adrenergic Receptor Signaling.

    Cell 161(5):1101 (2015) PMID 25981665 PMCID PMC4441853

    G-protein-coupled receptors (GPCRs) transduce signals from the extracellular environment to intracellular proteins. To gain structural insight into the regulation of receptor cytoplasmic conformations by extracellular ligands during signaling, we examine the structural dynamics of the cytoplasmi...
  2. A comparison of chemical shift sensitivity of trifluoromethyl tags: optimizing resolution in ¹⁹F NMR studies of proteins.

    Journal of Biomolecular NMR 62(1):97 (2015) PMID 25813845

    The elucidation of distinct protein conformers or states by fluorine ((19)F) NMR requires fluorinated moieties whose chemical shifts are most sensitive to subtle changes in the local dielectric and magnetic shielding environment. In this study we evaluate the effective chemical shift dispersion ...
  3. Conformational selection and functional dynamics of calmodulin: a (19)F nuclear magnetic resonance study.

    Biochemistry (Washington) 53(36):5727 (2014) PMID 25148136

    Calcium-bound calmodulin (CaM-4Ca(2+)) is innately promiscuous with regard to its protein interaction network within the cell. A key facet of the interaction process involves conformational selection. In the absence of a binding peptide, CaM-4Ca(2+) adopts an equilibrium between a native state (...
  4. Conformational selection and functional dynamics of calmodulin: a (19)F nuclear magnetic resonance study.

    Biochemistry (Washington) 53(36):5727 (2014) PMID 25148136

    Calcium-bound calmodulin (CaM-4Ca(2+)) is innately promiscuous with regard to its protein interaction network within the cell. A key facet of the interaction process involves conformational selection. In the absence of a binding peptide, CaM-4Ca(2+) adopts an equilibrium between a native state (...
  5. New pipelines for novel allosteric GPCR modulators.

    Biophysical Journal 107(2):287 (2014) PMID 25028870 PMCID PMC4104044

  6. New pipelines for novel allosteric GPCR modulators.

    Biophysical Journal 107(2):287 (2014) PMID 25028870 PMCID PMC4104044

  7. New Pipelines for Novel Allosteric GPCR Modulators

    Biophysical Journal 107(2):287 (2014)

  8. Temperature and pressure based NMR studies of detergent micelle phase equilibria.

    Journal of Physical Chemistry B 118(21):5698 (2014) PMID 24801930

    Bulk thermodynamic and volumetric parameters (ΔGmic°, ΔHmic°, ΔSmic°, ΔCp,mic°, ΔVmic°, and Δκmic°) associated with the monomer–micelle equilibrium, were directly determined for a variety of common detergents [sodium n-dodecyl sulfate (SDS), n-dodecyl phosphocholine (DPC), n-dodecyl-β-d-maltosid...
  9. Temperature and pressure based NMR studies of detergent micelle phase equilibria.

    Journal of Physical Chemistry B 118(21):5698 (2014) PMID 24801930

    Bulk thermodynamic and volumetric parameters (ΔGmic°, ΔHmic°, ΔSmic°, ΔCp,mic°, ΔVmic°, and Δκmic°) associated with the monomer–micelle equilibrium, were directly determined for a variety of common detergents [sodium n-dodecyl sulfate (SDS), n-dodecyl phosphocholine (DPC), n-dodecyl-β-d-maltosid...
  10. ¹⁹F NMR studies of a desolvated near-native protein folding intermediate.

    Biochemistry (Washington) 52(34):5780 (2013) PMID 23906334

    Although many proteins are recognized to undergo folding via an intermediate, the microscopic nature of folding intermediates is less understood. In this study, ¹⁹F NMR and near-UV circular dichroism (CD) are used to characterize a transition to a thermal folding intermediate of calmodulin, a wa...
  11. ¹⁹F NMR studies of a desolvated near-native protein folding intermediate.

    Biochemistry (Washington) 52(34):5780 (2013) PMID 23906334

    Although many proteins are recognized to undergo folding via an intermediate, the microscopic nature of folding intermediates is less understood. In this study, ¹⁹F NMR and near-UV circular dichroism (CD) are used to characterize a transition to a thermal folding intermediate of calmodulin, a wa...
  12. Dynamic equilibria between monomeric and oligomeric misfolded states of the mammalian prion protein measured by 19F NMR.

    Journal of the American Chemical Society 135(28):10533 (2013) PMID 23781904

    The assembly of misfolded proteins is a critical step in the pathogenesis of amyloid and prion diseases, although the molecular mechanisms underlying this phenomenon are not completely understood. Here, we use (19)F NMR spectroscopy to examine the thermodynamic driving forces surrounding formati...
  13. Dynamic equilibria between monomeric and oligomeric misfolded states of the mammalian prion protein measured by 19F NMR.

    Journal of the American Chemical Society 135(28):10533 (2013) PMID 23781904

    The assembly of misfolded proteins is a critical step in the pathogenesis of amyloid and prion diseases, although the molecular mechanisms underlying this phenomenon are not completely understood. Here, we use (19)F NMR spectroscopy to examine the thermodynamic driving forces surrounding formati...
  14. The role of ligands on the equilibria between functional states of a G protein-coupled receptor.

    Journal of the American Chemical Society 135(25):9465 (2013) PMID 23721409 PMCID PMC3763947

    G protein-coupled receptors exhibit a wide variety of signaling behaviors in response to different ligands. When a small label was incorporated on the cytosolic interface of transmembrane helix 6 (Cys-265), (19)F NMR spectra of the β2 adrenergic receptor (β2AR) reconstituted in maltose/neopentyl...
  15. The role of ligands on the equilibria between functional states of a G protein-coupled receptor.

    Journal of the American Chemical Society 135(25):9465 (2013) PMID 23721409 PMCID PMC3763947

    G protein-coupled receptors exhibit a wide variety of signaling behaviors in response to different ligands. When a small label was incorporated on the cytosolic interface of transmembrane helix 6 (Cys-265), (19)F NMR spectra of the β2 adrenergic receptor (β2AR) reconstituted in maltose/neopentyl...
  16. Effects of a polar amino acid substitution on helix formation and aggregate size along the detergent-induced peptide folding pathway

    Biochimica et Biophysica Acta (BBA) - Biomembranes 1828(2):373 (2013)

    Membrane proteins constitute a significant fraction of the proteome and are important drug targets. While the transmembrane (TM) segments of these proteins are primarily composed of hydrophobic residues, the inclusion of polar residues—either naturally occurring or as a consequence of ...
  17. Effects of a polar amino acid substitution on helix formation and aggregate size along the detergent-induced peptide folding pathway.

    Biochimica et Biophysica Acta 1828(2):373 (2013) PMID 23031573

    Membrane proteins constitute a significant fraction of the proteome and are important drug targets. While the transmembrane (TM) segments of these proteins are primarily composed of hydrophobic residues, the inclusion of polar residues-either naturally occurring or as a consequence of a disease-...
  18. The Dynamic Process of β2-Adrenergic Receptor Activation

    Cell 152(3):532 (2013)

    G-protein-coupled receptors (GPCRs) can modulate diverse signaling pathways, often in a ligand-specific manner. The full range of functionally relevant GPCR conformations is poorly understood. Here, we use NMR spectroscopy to characterize the conformational dynamics of the transmembran...
  19. The dynamic process of β(2)-adrenergic receptor activation.

    Cell 152(3):532 (2013) PMID 23374348 PMCID PMC3586676

    G-protein-coupled receptors (GPCRs) can modulate diverse signaling pathways, often in a ligand-specific manner. The full range of functionally relevant GPCR conformations is poorly understood. Here, we use NMR spectroscopy to characterize the conformational dynamics of the transmembrane core of ...
  20. The dynamic process of β(2)-adrenergic receptor activation.

    Cell 152(3):532 (2013) PMID 23374348 PMCID PMC3586676

    G-protein-coupled receptors (GPCRs) can modulate diverse signaling pathways, often in a ligand-specific manner. The full range of functionally relevant GPCR conformations is poorly understood. Here, we use NMR spectroscopy to characterize the conformational dynamics of the transmembrane core of ...