Stanley Opella
NMR structural studies of proteins in membranes and other supramolecular assemblies
NMR structural studies of proteins in membranes and other supramolecular assemblies
Contact Information
Professor of Chemistry and Biochemistry
Office: Natural Sciences Bldg 3121
Phone: 858-822-4820
Email: sopella@ucsd.edu
Group: View group members
Office: Natural Sciences Bldg 3121
Phone: 858-822-4820
Email: sopella@ucsd.edu
Group: View group members
Education
1974 Ph.D., , Stanford University
1969 B.S., , University of Kentucky
1974 Ph.D., , Stanford University
1969 B.S., , University of Kentucky
Awards and Academic Honors
1976-2000
Professor of Chemistry, University of Pennsylvania
1975-1976
Postdoctoral Fellow, M.I.T.
Research Interests
The overall goal of the research program is to develop protein expression systems, instrumentation, and experimental methods so that NMR spectroscopy can be used to study all of the proteins encoded in a genome. Substantial progress has been made through the development of high-resolution solid-state NMR methods, and it is now possible obtain completely resolved and assigned spectra of proteins in membrane bilayers and virus particles.
Membrane proteins are of particular interest, since they constitute about 30% of a genome, representing a major area of research in structural biology, and present challenging systems for NMR spectroscopy. The HIV-1 accessory protein Vpu is one of the principal systems currently being investigated. Vpu has two biological functions that affect the virulence of AIDS. Like all of the other membrane proteins, it is being studied in parallel by solution NMR and solid-state NMR methods. In its phosphorylated form, Vpu enhances both the processing of the envelope glycoprotein gp160, and the degradation of CD4 molecules in infected cells. The protein also acts as an ion channel, an activity associated with its trans-membrane helix and related to its ability to enhance the budding of new virus particles. Several other membrane proteins are under investigation, including the membrane proteins MerF and MerT responsible for transporting mercury across membranes into the cytoplasm where it is reduced to non-toxic and volatile metallic mercury.
Studies of filamentous bacteriophages provide opportunities to apply NMR spectroscopy to coat proteins in virus particles including those that display peptides on their surface.
Membrane proteins are of particular interest, since they constitute about 30% of a genome, representing a major area of research in structural biology, and present challenging systems for NMR spectroscopy. The HIV-1 accessory protein Vpu is one of the principal systems currently being investigated. Vpu has two biological functions that affect the virulence of AIDS. Like all of the other membrane proteins, it is being studied in parallel by solution NMR and solid-state NMR methods. In its phosphorylated form, Vpu enhances both the processing of the envelope glycoprotein gp160, and the degradation of CD4 molecules in infected cells. The protein also acts as an ion channel, an activity associated with its trans-membrane helix and related to its ability to enhance the budding of new virus particles. Several other membrane proteins are under investigation, including the membrane proteins MerF and MerT responsible for transporting mercury across membranes into the cytoplasm where it is reduced to non-toxic and volatile metallic mercury.
Studies of filamentous bacteriophages provide opportunities to apply NMR spectroscopy to coat proteins in virus particles including those that display peptides on their surface.
Primary Research Area
Biochemistry
Biochemistry
Interdisciplinary interests
Biophysics
Macromolecular Structure
Macromolecular Structure
Image Gallery
Three dimensional structure of the mercury transport membrane protein MerFt determined by solid-state NMR spectroscopy in phospholipid bilayers (DeAngelis et al, 2006).
Comparison of the two-dimensional solid-state NMR spectra and the three-dimensionial structures determined from these data for the "low" and "high" temperature forms of the coat protein in the filamentous bacteriophage Pf1 (Thiriot et al, 2005).
Pulse sequence for a newly developed solid-state NMR experiments. PISEMO (polarization inversion spin exchange-modulated observation) provides high sensitivity through detection of the proton signals (Wu and Opella, 2007).
Three dimensional structure of the mercury transport membrane protein MerFt determined by solid-state NMR spectroscopy in phospholipid bilayers (DeAngelis et al, 2006).
Comparison of the two-dimensional solid-state NMR spectra and the three-dimensionial structures determined from these data for the "low" and "high" temperature forms of the coat protein in the filamentous bacteriophage Pf1 (Thiriot et al, 2005).
Pulse sequence for a newly developed solid-state NMR experiments. PISEMO (polarization inversion spin exchange-modulated observation) provides high sensitivity through detection of the proton signals (Wu and Opella, 2007).
Selected Publications
- Wu CH, Opella SJ, "Proton-detected separated local field spectroscopy.", J Magn Reson, 2008, 1, 165-70 [View Abstract]
- De Angelis AA, Opella SJ, "Bicelle samples for solid-state NMR of membrane proteins.", Nat Protoc, 2007, 10, 2332-8 [View Abstract]
- Nevzorov AA, Opella SJ, "Selective averaging for high-resolution solid-state NMR spectroscopy of aligned samples.", J Magn Reson, 2007, 1, 59-70 [View Abstract]
- Park SH, Opella SJ, "Conformational changes induced by a single amino acid substitution in the trans-membrane domain of Vpu: implications for HIV-1 susceptibility to channel blocking drugs.", Protein Sci, 2007, 10, 2205-15 [View Abstract]
- Sinha N, Grant CV, Park SH, Brown JM, Opella SJ, "Triple resonance experiments for aligned sample solid-state NMR of (13)C and (15)N labeled proteins.", J Magn Reson, 2007, 1, 51-64 [View Abstract]
- De Angelis AA, Howell SC, Nevzorov AA, Opella SJ, "Structure determination of a membrane protein with two trans-membrane helices in aligned phospholipid bicelles by solid-state NMR spectroscopy.", J Am Chem Soc, 2006, 37, 12256-67 [View Abstract]
- Park SH, Prytulla S, De Angelis AA, Brown JM, Kiefer H, Opella SJ, "High-resolution NMR spectroscopy of a GPCR in aligned bicelles.", J Am Chem Soc, 2006, 23, 7402-3 [View Abstract]
- Howell SC, Mesleh MF, Opella SJ, "NMR structure determination of a membrane protein with two transmembrane helices in micelles: MerF of the bacterial mercury detoxification system.", Biochemistry, 2005, 13, 5196-206 [View Abstract]
- Park SH, Opella SJ, "Tilt angle of a trans-membrane helix is determined by hydrophobic mismatch.", J Mol Biol, 2005, 2, 310-8 [View Abstract]
- Thiriot DS, Nevzorov AA, Opella SJ, "Structural basis of the temperature transition of Pf1 bacteriophage.", Protein Sci, 2005, 4, 1064-70 [View Abstract]