Stanley J Opella

University of California, San Diego, San Diego, California, United States

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Publications (267)1029.59 Total impact

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    Journal of Biomolecular NMR 08/2014; · 2.85 Impact Factor
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    Jasmina Radoicic, George J Lu, Stanley J Opella
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    ABSTRACT: Membrane proteins have always presented technical challenges for structural studies because of their requirement for a lipid environment. Multiple approaches exist including X-ray crystallography and electron microscopy that can give significant insights into their structure and function. However, nuclear magnetic resonance (NMR) is unique in that it offers the possibility of determining the structures of unmodified membrane proteins in their native environment of phospholipid bilayers under physiological conditions. Furthermore, NMR enables the characterization of the structure and dynamics of backbone and side chain sites of the proteins alone and in complexes with both small molecules and other biopolymers. The learning curve has been steep for the field as most initial studies were performed under non-native environments using modified proteins until ultimately progress in both techniques and instrumentation led to the possibility of examining unmodified membrane proteins in phospholipid bilayers under physiological conditions. This review aims to provide an overview of the development and application of NMR to membrane proteins. It highlights some of the most significant structural milestones that have been reached by NMR spectroscopy of membrane proteins, especially those accomplished with the proteins in phospholipid bilayer environments where they function.
    Quarterly Reviews of Biophysics 07/2014; · 11.88 Impact Factor
  • Bibhuti B Das, Sang Ho Park, Stanley J Opella
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    ABSTRACT: The motional averaging of powder pattern lineshapes is one of the most fundamental aspects of sold-state NMR. Since membrane proteins in liquid crystalline phospholipid bilayers undergo fast rotational diffusion, all of the signals reflect the angles of the principal axes of their dipole-dipole and chemical shift tensors with respect to the axis defined by the bilayer normal. The frequency span and sign of the axially symmetric powder patterns that result from motional averaging about a common axis provide sufficient structural restraints for the calculation of the three-dimensional structure of a membrane protein in a phospholipid bilayer environment. The method is referred to as rotationally aligned (RA) solid-state NMR and demonstrated with results on full-length, unmodified membrane proteins with one, two, and seven trans-membrane helices. RA solid-state NMR is complementary to other MAS solid-state NMR methods, in particular oriented sample (OS) solid-state NMR of stationary, aligned samples. Structural distortions of membrane proteins from the truncations of terminal residues and other sequence modifications, and the use of detergent micelles instead of phospholipid bilayers have also been demonstrated. Thus, it is highly advantageous to determine the structures of unmodified membrane proteins in liquid crystalline phospholipid bilayers under physiological conditions. RA solid-state NMR provides a general method for obtaining accurate and precise structures of membrane proteins under near-native conditions. This article is part of a Special Issue entitled: NMR Spectroscopy for Atomistic Views of Biomembranes and Cell Surfaces.
    Biochimica et Biophysica Acta 04/2014; · 4.66 Impact Factor
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    ABSTRACT: The benefits of protein structure refinement in water are well documented. However, performing structure refinement with explicit atomic representation of the solvent molecules is computationally expensive and impractical for NMR-restrained structure calculations that start from completely extended polypeptide templates. Here we describe a new implicit solvation potential, EEFx (Effective Energy Function for XPLOR-NIH), for NMR-restrained structure calculations of proteins in XPLOR-NIH. The key components of EEFx are an energy term for solvation energy that works together with other nonbonded energy functions, and a dedicated force field for conformational and nonbonded protein interaction parameters. The initial results obtained with EEFx show that significant improvements in structural quality can be obtained. EEFx is computationally efficient and can be used both to fold and refine structures. Overall, EEFx improves the quality of protein conformation and nonbonded atomic interactions. Moreover, such benefits are accompanied by enhanced structural precision and enhanced structural accuracy, reflected in improved agreement with the cross-validated dipolar coupling data. Finally, implementation of EEFx calculations is straightforward and computationally efficient. Overall, EEFx provides a useful method for the practical calculation of experimental protein structures in a physically realistic environment.
    Journal of Magnetic Resonance 04/2014; 243C:54-64. · 2.30 Impact Factor
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    George J Lu, Stanley J Opella
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    ABSTRACT: In the stationary, aligned samples used in oriented sample (OS) solid-state NMR, (1)H-(1)H homonuclear dipolar couplings are not attenuated as they are in magic angle spinning solid-state NMR; consequently, they are available for participation in dipolar coupling-based spin-exchange processes. Here we describe analytically the pathways of (15)N-(15)N spin-exchange mediated by (1)H-(1)H homonuclear dipolar couplings. The mixed-order proton-relay mechanism can be differentiated from the third spin assisted recoupling mechanism by setting the (1)H to an off-resonance frequency so that it is at the "magic angle" during the spin-exchange interval in the experiment, since the "magic angle" irradiation nearly quenches the former but only slightly attenuates the latter. Experimental spectra from a single crystal of N-acetyl leucine confirm that this proton-relay mechanism plays the dominant role in (15)N-(15)N dilute-spin-exchange in OS solid-state NMR in crystalline samples. Remarkably, the "forbidden" spin-exchange condition under "magic angle" irradiation results in (15)N-(15)N cross-peaks intensities that are comparable to those observed with on-resonance irradiation in applications to proteins. The mechanism of the proton relay in dilute-spin-exchange is crucial for the design of polarization transfer experiments.
    The Journal of Chemical Physics 03/2014; 140(12):124201. · 3.12 Impact Factor
  • Bibhuti B Das, Hua Zhang, Stanley J Opella
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    ABSTRACT: A method for making resonance assignments in magic angle spinning solid-state NMR spectra of membrane proteins that utilizes the range of heteronuclear dipolar coupling frequencies in combination with conventional chemical shift based assignment methods is demonstrated. The Dipolar Assisted Assignment Protocol (DAAP) takes advantage of the rotational alignment of the membrane proteins in liquid crystalline phospholipid bilayers. Improved resolution is obtained by combining the magnetically inequivalent heteronuclear dipolar frequencies with isotropic chemical shift frequencies. Spectra with both dipolar and chemical shift frequency axes assist with resonance assignments. DAAP can be readily extended to three- and four-dimensional experiments and to include both backbone and side chain sites in proteins.
    Journal of Magnetic Resonance 03/2014; 242C:224-232. · 2.30 Impact Factor
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    ABSTRACT: While antimicrobial peptides (AMPs) have been widely investigated as potential therapeutics, high resolution structures obtained under biologically relevant conditions are lacking. Here, the high-resolution structures of the homologous 22-residue long AMPs piscidin 1 (p1) and piscidin 3 (p3) are determined in fluid-phase 3:1 phosphatidylcholine/phosphatidylglycerol (PC/PG) and 1:1 phosphatidylethanolamine/phosphatidylglycerol (PE/PG) bilayers to identify molecular features important for membrane destabilization in bacterial cell membrane mimics. Structural refinement of (1)H-(15)N dipolar couplings and (15)N chemical shifts measured by oriented sample solid-state NMR and all-atom molecular dynamics (MD) simulations provide structural and orientational information of high precision and accuracy about these interfacially-bound α-helical peptides. The tilt of the helical axis, τ, is between 83° and 93° with respect to the bilayer normal for all systems and analysis methods. The average azimuthal rotation, ρ, is 235°, which results in burial of hydrophobic residues in the bilayer. The refined NMR and MD structures reveal a slight kink at G13 that delineates two helical segments characterized by a small difference in their τ angles (<10°) and significant difference in their ρ angles (~25°). Remarkably, the kink, at the end of a G(X)4G motif highly conserved among members of the piscidin family, allows p1 and p3 to adopt ρ angles that maximize their hydrophobic moments. Two structural features differentiate the more potent p1 from p3: p1 has a larger ρ angle and less N-terminal fraying. The peptides have comparable depths of insertion in PC/PG but p3 is 2Å more deeply inserted than p1 in PE/PG. In contrast to the ideal α-helical structures typically assumed in mechanistic models of AMPs, p1 and p3 adopt disrupted α-helical backbones that correct for differences in the amphipathicity of their N- and C-ends, and their centers of mass lie approximately 1.2-3.6 Å below the plane defined by the C2 atoms of the lipid acyl chains.
    Journal of the American Chemical Society 01/2014; · 10.68 Impact Factor
  • C.H. Wu, Anna A. De Angelis, Stanley J. Opella
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    ABSTRACT: The efficiency and selectivity of SPECIFIC-CP, a widely used method for selective double cross-polarization in triple-resonance magic angle spinning solid-state NMR, is improved by performing the tangential-shaped (13)C irradiation at an offset frequency that meets the Lee-Goldburg condition (LG-SPECIFIC-CP). This is demonstrated on polycrystalline samples of uniformly (13)C, (15)N labeled N-acetyl-leucine and N-formyl-Met-Leu-Phe-OH (MLF) at 700MHz and 900MHz (1)H resonance frequencies, respectively. For the single (13)Cα of N-acetyl-leucine, relative to conventional broad band cross-polarization, the SPECIFIC-CP signal has 47% of the intensity. Notably, the LG-SPECIFIC-CP signal has 72% of the intensity, essentially the theoretical maximum. There were no other changes in the experimental parameters. The three (13)Cα signals in MLF show some variation in intensities, reflecting the relatively narrow bandwidth of a frequency-offset procedure, and pointing to future developments for this class of experiment.
    Journal of Magnetic Resonance. 01/2014;
  • Bibhuti B. Das, Stanley J. Opella
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    ABSTRACT: Multiple acquisition spectroscopy (MACSY) experiments that enable multiple free induction decays to be recorded during individual experiments are demonstrated. In particular, the experiments incorporate separated local field spectroscopy into homonuclear and heteronuclear correlation spectroscopy. The measured heteronuclear dipolar couplings are valuable in structure determination as well as in enhancing resolution by providing an additional frequency axis. In one example four different three-dimensional spectra are obtained in a single experiment, demonstrating that substantial potential saving in experimental time is available when multiple multi-dimensional spectra are required as part of solid-state NMR studies.
    Journal of Magnetic Resonance. 01/2014;
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    ABSTRACT: Acyl carrier protein (ACP) transports the growing fatty acid chain between enzymatic domains of fatty acid synthase (FAS) during biosynthesis. Because FAS enzymes operate on ACP-bound acyl groups, ACP must stabilize and transport the growing lipid chain. ACPs have a central role in transporting starting materials and intermediates throughout the fatty acid biosynthetic pathway. The transient nature of ACP-enzyme interactions impose major obstacles to obtaining high-resolution structural information about fatty acid biosynthesis, and a new strategy is required to study protein-protein interactions effectively. Here we describe the application of a mechanism-based probe that allows active site-selective covalent crosslinking of AcpP to FabA, the Escherichia coli ACP and fatty acid 3-hydroxyacyl-ACP dehydratase, respectively. We report the 1.9 Å crystal structure of the crosslinked AcpP-FabA complex as a homodimer in which AcpP exhibits two different conformations, representing probable snapshots of ACP in action: the 4'-phosphopantetheine group of AcpP first binds an arginine-rich groove of FabA, then an AcpP helical conformational change locks AcpP and FabA in place. Residues at the interface of AcpP and FabA are identified and validated by solution nuclear magnetic resonance techniques, including chemical shift perturbations and residual dipolar coupling measurements. These not only support our interpretation of the crystal structures but also provide an animated view of ACP in action during fatty acid dehydration. These techniques, in combination with molecular dynamics simulations, show for the first time that FabA extrudes the sequestered acyl chain from the ACP binding pocket before dehydration by repositioning helix III. Extensive sequence conservation among carrier proteins suggests that the mechanistic insights gleaned from our studies may be broadly applicable to fatty acid, polyketide and non-ribosomal biosynthesis. Here the foundation is laid for defining the dynamic action of carrier-protein activity in primary and secondary metabolism, providing insight into pathways that can have major roles in the treatment of cancer, obesity and infectious disease.
    Nature 12/2013; · 38.60 Impact Factor
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    George J Lu, Stanley J Opella
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    ABSTRACT: Oriented sample solid-state NMR spectroscopy can be used to determine the three-dimensional structures of membrane proteins in magnetically or mechanically aligned lipid bilayers. The bottleneck for applying this technique to larger and more challenging proteins is making resonance assignments, which is conventionally accomplished through the preparation of multiple selectively isotopically labeled samples and performing an analysis of residues in regular secondary structure based on Polarity Index Slant Angle (PISA) Wheels and Dipolar Waves. Here we report the complete resonance assignment of the full-length mercury transporter, MerF, an 81-residue protein, which is challenging because of overlapping PISA Wheel patterns from its two trans-membrane helices, by using a combination of solid-state NMR techniques that improve the spectral resolution and provide correlations between residues and resonances. These techniques include experiments that take advantage of the improved resolution of the MSHOT4-Pi4/Pi pulse sequence; the transfer of resonance assignments through frequency alignment of heteronuclear dipolar couplings, or through dipolar coupling correlated isotropic chemical shift analysis; (15)N/(15)N dilute spin exchange experiments; and the use of the proton-evolved local field experiment with isotropic shift analysis to assign the irregular terminal and loop regions of the protein, which is the major "blind spot" of the PISA Wheel/Dipolar Wave method.
    Journal of Biomolecular NMR 12/2013; · 2.85 Impact Factor
  • Eugene C Lin, Stanley J Opella
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    ABSTRACT: Covariance spectroscopy (COV), a statistical method that provides increased sensitivity, can be applied to two-dimensional high-resolution solid-state NMR experiments, such as homonuclear spin-exchange spectroscopy. We the alternative States sampling scheme to the experimental time by 50%. By combining COV with other processing methods for non-uniform sampling (NUS), many different three-dimensional experiments can be performed with substantial increases in overall sensitivity. As an example, we show a three-dimensional homonuclear spin-exchange/separated-local-field (SLF) spectrum that enables the assignment of resonances and the measurement of structural restraints from a single experiment performed in a limited amount of time.
    Journal of Magnetic Resonance 12/2013; 239C:57-60. · 2.30 Impact Factor
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    ABSTRACT: Two-dimensional (15)N chemical shift/(1)H chemical shift and three-dimensional (1)H-(15)N dipolar coupling/(15)N chemical shift/(1)H chemical shift MAS solid-state NMR correlation spectra of the filamentous bacteriophage Pf1 major coat protein show single-site resolution in noncrystalline, intact-phage preparations. The high sensitivity and resolution result from (1)H detection at 600MHz under 50kHz magic angle spinning using ∼0.5mg of perdeuterated and uniformly (15)N-labeled protein in which the exchangeable amide sites are partially or completely back-exchanged (reprotonated). Notably, the heteronuclear (1)H-(15)N dipolar coupling frequency dimension is shown to select among (15)N resonances, which will be useful in structural studies of larger proteins where the resonances exhibit a high degree of overlap in multidimensional chemical shift correlation spectra.
    Journal of Magnetic Resonance 10/2013; 237C:164-168. · 2.30 Impact Factor
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    ABSTRACT: Hydrophobic membrane-spanning helices often are flanked by interfacial aromatic or charged residues. In this paper we compare the consequences of single Trp → Tyr substitutions at each interface for the properties of a defined transmembrane helix, in the absence of charged residues. The choice of molecular framework is critical for these single-residue experiments, because the presence of "too many" aromatic residues (more than one at either membrane-water interface) introduces excess dynamic averaging of solid-state NMR observables. To this end, we compare the outcomes when changing W5 or W19, or both of them, to tyrosine in the well characterized transmembrane peptide acetyl-GGALW(5)(LA)6LW(19)LAGA-amide ("GWALP23"). By means of solid-state (2)H and (15)N NMR experiments, we find that Y(19)GW(5)ALP23 displays similar magnitudes of peptide helix tilt as Y(5)GW(19)ALP23 and responds similarly to changes in bilayer thickness, from DLPC to DMPC to DOPC. The presence of Y19 changes the azimuthal rotation angle ρ (about the helix axis) to a similar extent as Y5, but in the opposite direction. When tyrosines are substituted for both tryptophans to yield GY(5,19)ALP23, the helix tilt angle is again of comparable magnitude, and furthermore the preferred azimuthal rotation angle ρ is relatively unchanged from that of GW(5,19)ALP23. The extent of dynamic averaging increases marginally when Tyr replaces Trp. Yet, importantly, all members of the peptide family having single Tyr or Trp residues near each interface exhibit only moderate and not highly extensive dynamic averaging. The results provide important benchmarks for evaluating conformational and dynamic control of membrane protein function.
    The Journal of Physical Chemistry B 10/2013; · 3.61 Impact Factor
  • Yan Wang, Sang Ho Park, Ye Tian, Stanley J Opella
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    ABSTRACT: Abstract The role of histidine in channel-forming transmembrane (TM) helices was investigated by comparing the TM helices from Virus protein 'u' (Vpu) and the M2 proton channel. Both proteins are members of the viroporin family of small membrane proteins that exhibit ion channel activity, and have a single TM helix that is capable of forming oligomers. The TM helices from both proteins have a conserved tryptophan towards the C-terminus. Previously, alanine 18 of Vpu was mutated to histidine in order to artificially introduce the same HXXXW motif that is central to the proton channel activity of M2. Interestingly, the mutated Vpu TM resulted in an increase in helix tilt angle of 11° in lipid bilayers compared to the wild-type Vpu TM. Here, we find the reverse, when histidine 37 of the HXXXW motif in M2 was mutated to alanine, it decreased the helix tilt by 10° from that of wild-type M2. The tilt change is independent of both the helix length and the presence of tryptophan. In addition, compared to wild-type M2, the H37A mutant displayed lowered sensitivity to proton concentration. We also found that the solvent accessibility of histidine-containing M2 is greater than without histidine. This suggests that the TM helix may increase the solvent exposure by changing its tilt angle in order to accommodate a polar/charged residue within the hydrophobic membrane region. The comparative results of M2, Vpu and their mutants demonstrated the significance of histidine in a transmembrane helix and the remarkable plasticity of the function and structure of ion channels stemming from changes at a single amino acid site.
    Molecular Membrane Biology 10/2013; · 3.13 Impact Factor
  • Eugene C Lin, Stanley J Opella
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    ABSTRACT: We describe the incorporation of non-uniform sampling (NUS) compressed sensing (CS) into oriented sample (OS) solid-state NMR for stationary aligned samples and magic angle spinning (MAS) Solid-state NMR for unoriented 'powder' samples. Both simulated and experimental results indicate that 25-33% of a full linearly sampled data set is required to reconstruct two- and three-dimensional solid-state NMR spectra with high fidelity. A modest increase in signal-to-noise ratio accompanies the reconstruction.
    Journal of Magnetic Resonance 10/2013; 237C:40-48. · 2.30 Impact Factor
  • Bibhuti B Das, Eugene C Lin, Stanley J Opella
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    ABSTRACT: Structure determination by solid-state NMR of proteins is rapidly advancing as result of recent developments of samples, experimental methods, and calculations. There are a number of different solid-state NMR approaches that utilize stationary, aligned samples or magic angle spinning of unoriented 'powder' samples, and depending on the sample and the experimental method can emphasize the measurement of distances or angles, ideally both, as sources of structural constraints. Multi-dimensional correlation spectroscopy of low-gamma nuclei such as 15N and 13C is an important step for making resonance assignments and measurements of angular restraints in membrane proteins. However, the efficiency of coherence transfer predominantly depends upon the strength of dipole-dipole interaction, and this can vary from site to site and between sample alignments, for example, during the mixing of 13C and 15N magnetization in stationary aligned and in magic angle spinning samples. Here, we demonstrate that the efficiency of polarization transfer can be improved by using adiabatic demagnetization and remagnetization techniques on stationary aligned samples; and proton assisted insensitive nuclei cross-polarization in magic angle sample spinning samples. Adiabatic cross-polarization technique provides an alternative mechanism for spin-diffusion experiments correlating 15N/15N and 15N/13C chemical shifts over large distances. Improved efficiency in cross-polarization with 40% - 100% sensitivity enhancements are observed in proteins and single crystals, respectively. We describe solid-state NMR experimental techniques that are optimal for membrane proteins in liquid crystalline phospholipid bilayers under physiological conditions. The techniques are illustrated with data from both single crystals of peptides and of membrane proteins in phospholipid bilayers.
    The Journal of Physical Chemistry B 09/2013; · 3.61 Impact Factor
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    George J Lu, Stanley J Opella
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    ABSTRACT: One of the main applications of solid-state NMR is to study the structure and dynamics of biopolymers, such as membrane proteins, under physiological conditions where the polypeptides undergo global motions as they do in biological membranes. The effects of NMR radiofrequency irradiations on nuclear spins are strongly influenced by these motions. For example, we previously showed that the MSHOT-Pi4 pulse sequence yields spectra with resonance line widths about half of those observed using the conventional pulse sequence when applied to membrane proteins undergoing rapid uniaxial rotational diffusion in phospholipid bilayers. In contrast, the line widths were not changed in microcrystalline samples where the molecules did not undergo global motions. Here, we demonstrate experimentally and describe analytically how some Hamiltonian terms are susceptible to sample motions, and it is their removal through the critical π∕2 Z-rotational symmetry that confers the "motion adapted" property to the MSHOT-Pi4 pulse sequence. This leads to the design of separated local field pulse sequence "Motion-adapted SAMPI4" and is generalized to an approach for the design of decoupling sequences whose performance is superior in the presence of molecular motions. It works by cancelling the spin interaction by explicitly averaging the reduced Wigner matrix to zero, rather than utilizing the 2π nutation to average spin interactions. This approach is applicable to both stationary and magic angle spinning solid-state NMR experiments.
    The Journal of Chemical Physics 08/2013; 139(8):084203. · 3.12 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) protein p7 plays an important role in the assembly and release of mature virus particles. This small 63-residue membrane protein has been shown to induce channel activity, which may contribute to its functions. p7 is highly conserved throughout the entire range of HCV genotypes, which contributes to making p7 a potential target for antiviral drugs. The secondary structure of p7 from the J4 genotype and the tilt angles of the helices within bilayers have been previously characterized by nuclear magnetic resonance (NMR). Here we describe the three-dimensional structure of p7 in short chain phospholipid (1,2-dihexanoyl-sn-glycero-3-phosphocholine) micelles, which provide a reasonably effective membrane-mimicking environment that is compatible with solution NMR experiments. Using a combination of chemical shifts, residual dipolar couplings, and PREs, we determined the structure of p7 using an implicit membrane potential combining both CS-Rosetta decoys and Xplor-NIH refinement. The final set of structures has a backbone root-mean-square deviation of 2.18 Å. Molecular dynamics simulations in NAMD indicate that several side chain interactions might be taking place and that these could affect the dynamics of the protein. In addition to probing the dynamics of p7, we evaluated several drug–protein and protein–protein interactions. Established channel-blocking compounds such as amantadine, hexamethylene amiloride, and long alkyl chain iminosugar derivatives inhibit the ion channel activity of p7. It has also been shown that the protein interacts with HCV nonstructural protein 2 at the endoplasmic reticulum and that this interaction may be important for the infectivity of the virus. Changes in the chemical shift frequencies of solution NMR spectra identify the residues taking part in these interactions.
    Biochemistry 07/2013; 52(31):5295–5303. · 3.38 Impact Factor
  • Stanley J Opella
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    ABSTRACT: One of the most important topics in experimental structural biology is determining the structures of membrane proteins. These structures represent one-third of all of the information expressed from a genome, distinguished by their locations within the phospholipid bilayer of cells, organelles, or enveloped viruses. Their highly hydrophobic nature and insolubility in aqueous media means that they require an amphipathic environment. They have unique functions in transport, catalysis, channel formation, and signaling. Researchers are particularly interested in G-protein coupled receptors (GPCRs) because they modulate many biological processes, and about half of the approximately 800 of these proteins within the human genome are or can be turned into drug receptors that affect a wide range of diseases. Because of experimental difficulties, researchers have studied membrane proteins using a wide variety of artificial media that mimic membranes, such as mixed organic solvents or detergents. More sophisticated mimics include bilayer discs (bicelles) and the lipid cubic phase (LCP), but both of these contain a very large detergent component, which can disrupt the stability and function of membrane proteins. To have confidence in the resulting structures and their biological functions and to avoid disrupting these delicate proteins, the structures of membrane proteins should be determined in their native environment of liquid crystalline phospholipid bilayers under physiological conditions. This Account describes a recently developed general method for determining the structures of unmodified membrane proteins in phospholipid bilayers by solid-state NMR spectroscopy. Because it relies on the natural, rapid rotational diffusion of these proteins about the bilayer normal, this method is referred to as rotationally aligned (RA) solid-state NMR. This technique elaborates on oriented sample (OS) solid-state NMR, its complementary predecessor. These methods exploit the power of solid-state NMR, which enables researchers to obtain well-resolved spectra from "immobile" membrane proteins in phospholipid bilayers, to separate and measure frequencies that reflect orientations with respect to the bilayer normal, and to make complementary distance measurements. The determination of the structures of several membrane proteins, most prominently the chemokine receptor CXCR1, a 350-residue GPCR, has demonstrated this approach.
    Accounts of Chemical Research 07/2013; · 20.83 Impact Factor

Publication Stats

6k Citations
1,029.59 Total Impact Points

Institutions

  • 2001–2014
    • University of California, San Diego
      • Department of Chemistry and Biochemistry
      San Diego, California, United States
  • 2011–2013
    • Sanford-Burnham Medical Research Institute
      La Jolla, California, United States
  • 2008–2012
    • University of Arkansas
      • Department of Chemistry and Biochemistry
      Fayetteville, AR, United States
  • 2009
    • University of South Carolina
      • Department of Computer Science & Engineering
      Columbia, SC, United States
  • 2006–2009
    • Florida State University
      • Department of Chemistry and Biochemistry
      Tallahassee, FL, United States
    • Harvard Medical School
      • Department of Neurology
      Boston, MA, United States
  • 2001–2008
    • CSU Mentor
      • Department of Chemistry and Biochemistry
      Long Beach, California, United States
  • 1979–2007
    • University of Pennsylvania
      • Department of Chemistry
      Philadelphia, PA, United States
  • 2005
    • University of Massachusetts Amherst
      Amherst Center, Massachusetts, United States
  • 2003
    • National University (California)
      San Diego, California, United States
  • 2002
    • University of Minnesota Twin Cities
      • Department of Chemistry
      Minneapolis, MN, United States
  • 1998–2002
    • Wistar Institute
      Philadelphia, Pennsylvania, United States
  • 1993–1994
    • William Penn University
      Philadelphia, Pennsylvania, United States