- Electron Spin Resonance Studies
- Photoreceptor and optogenetics research
- Receptor Mechanisms and Signaling
- Lipid Membrane Structure and Behavior
- Photosynthetic Processes and Mechanisms
- Lanthanide and Transition Metal Complexes
- Protein Structure and Dynamics
- Hemoglobin structure and function
- Spectroscopy and Quantum Chemical Studies
- Enzyme Structure and Function
- Nitric Oxide and Endothelin Effects
- Magnetism in coordination complexes
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- Advanced NMR Techniques and Applications
- Metal-Catalyzed Oxygenation Mechanisms
- Mass Spectrometry Techniques and Applications
- Ion channel regulation and function
- DNA and Nucleic Acid Chemistry
- Molecular spectroscopy and chirality
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Electrochemical Analysis and Applications
- Computational Drug Discovery Methods
- Advanced MRI Techniques and Applications
University of California, Los Angeles
2015-2024
Doheny Eye Institute
2014-2024
California Institute of Technology
2016
Pasadena City College
2016
University of California, Berkeley
1973-2015
Jean Hailes
2015
UCLA Health
2008-2014
Vanderbilt University
2007-2013
University of California System
2003-2011
Cornell University
2010
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular motion in spin-labeled phospholipids and membranesHarden M. McConnell Wayne L. HubbellCite this: J. Am. Chem. Soc. 1971, 93, 2, 314–326Publication Date (Print):January 1, 1971Publication History Published online1 May 2002Published inissue 1 January 1971https://pubs.acs.org/doi/10.1021/ja00731a005https://doi.org/10.1021/ja00731a005research-articleACS PublicationsRequest reuse permissionsArticle Views1210Altmetric-Citations1236LEARN ABOUT...
Conformational changes are thought to underlie the activation of heterotrimeric GTP-binding protein (G protein)—coupled receptors. Such in rhodopsin were explored by construction double cysteine mutants, each containing one at cytoplasmic end helix C and various positions F. Magnetic dipolar interactions between spin labels attached these residues revealed their proximity, interaction upon light suggested a rigid body movement helices relative another. Disulfide cross-linking prevented...
Thirty single cysteine substitution mutants of T4 lysozyme have been prepared and spin-labeled with a sulfhydryl-specific nitroxide reagent in order to systematically investigate the relationship between side-chain mobility protein structure. The perturbation caused by replacement native residue amino acid was assessed from resulting changes biological activity, circular dichroism, free energy folding. produced context-dependent stability activity similar those observed for natural acids at...
Site-directed spin labeling has qualitatively shown that a key event during activation of rhodopsin is rigid-body movement transmembrane helix 6 (TM6) at the cytoplasmic surface molecule. To place this result on quantitative footing, and to identify movements other helices upon photoactivation, double electron-electron resonance (DEER) spectroscopy was used determine distances distance changes between pairs nitroxide side chains introduced in rhodopsin. Sixteen were selected from set nine...
Ten mutants of bacteriorhodopsin, each containing a single cysteine residue regularly spaced along helix D and facing the lipid bilayer, were derivatized with nitroxide spin label. Collision rates apolar oxygen increased distance from membrane/solution interface. polar metal ion complexes decreased over same distance. Although collision depend on steric constraints imposed by local protein structure depth in membrane, ratio rate to those complex is independent structural features protein....
How a receptor transmits signal G protein–coupled receptors (GPCRs) transmit diverse external signals into the cell. When activated by an outside stimulus, they bind to protein inside cell and accelerate exchange of bound guanosine diphosphate (GDP) nucleotide for triphosphate, which initiates intercellular signaling. Dror et al. used atomic-level molecular dynamics simulations show how GPCRs enhance GDP release. The is dynamic frequently adopts conformation that exposes even without bound....
Redirection and acceleration of technological change through policy intervention is essential for addressing climate other sustainability challenges. We offer frameworks to conceptualize model ex ante how local interventions can ...To address global challenges, (public) are needed induce or accelerate change. While most occur on the level, their innovation effects spill over jurisdictions, ...
Abstract The µ-opioid receptor (µOR) is an important target for pain management 1 and molecular understanding of drug action on µOR will facilitate the development better therapeutics. Here we show, using double electron–electron resonance single-molecule fluorescence energy transfer, how ligand-specific conformational changes translate into a broad range intrinsic efficacies at transducer level. We identify several conformations cytoplasmic face that interconvert different timescales,...
Site-directed mutagenesis was used to produce mutants of bacteriorhodopsin where either glycine-72, threonine-90, leucine-92, or serine-169 replaced by a cysteine. Two different spin labels were then covalently attached these sites. The selection attachment sites covered two postulated loops (72,169) and membrane-spanning segment (90,92). It not possible properly refold the protein labeled at position 90, presumably due steric problems, but EPR spectra other that successfully reconstituted...
Thirty consecutive single cysteine substitution mutants in the amino acids Q225-I256 of bovine rhodopsin have been prepared and modified with a sulfhydryl specific nitroxide reagent. This sequence includes E-F interhelical loop, transducin interaction site. The accessibilities attached nitroxides to collisions hydrophilic hydrophobic paramagnetic probes solution were determined, electron resonance spectra analyzed terms side chain mobility, both dark after photoactivation. Accessibility cata...
Two single cysteine substitution mutants at helix surface sites in T4 lysozyme (D72C and V131C) have been modified with a series of nitroxide methanethiosulfonate reagents to investigate the structural dynamical origins their electron paramagnetic resonance spectra. The novel include 4-substituted derivatives either pyrroline or pyrrolidine nitroxides. spectral line shapes were analyzed as function side chain structure temperature using simulation method order parameter diffusion rates about...