Proton Detected Solid-State NMR of Membrane Proteins at 28 Tesla (1.2 GHz) and 100 kHz Magic-Angle Spinning

The available magnetic field strength for high resolution NMR in persistent superconducting magnets has recently improved from 23.5 to 28 Tesla, increasing the proton resonance frequency from 1 to 1.2 GHz. For magic-angle spinning (MAS) NMR, this is expected to improve resolution, provided the sample preparation results in homogeneous broadening. We compare two-dimensional (2D) proton detected MAS NMR spectra of four membrane proteins at 950 and 1200 MHz. We find a consistent improvement in resolution that scales superlinearly with the increase in magnetic field for three of the four examples. In 3D and 4D spectra, which are now routinely acquired, this improvement indicates the ability to resolve at least 2 and 2.5 times as many signals, respectively.

[1]  R. Glockshuber,et al.  Biomolecular solid-state NMR spectroscopy at highest field: the gain in resolution at 1200 MHz , 2021, bioRxiv.

[2]  L. Andreas,et al.  Transferred-Rotational-Echo Double Resonance , 2021, The journal of physical chemistry. A.

[3]  B. Reif,et al.  Impact of Magnetic Field Strength on Resolution and Sensitivity of Proton Resonances in Biological Solids , 2020 .

[4]  B. Meier,et al.  Protein NMR Spectroscopy at 150 kHz Magic‐Angle Spinning Continues To Improve Resolution and Mass Sensitivity , 2020, Chembiochem : a European journal of chemical biology.

[5]  B. Reif,et al.  MAS dependent sensitivity of different isotopomers in selectively methyl protonated protein samples in solid state NMR , 2019, Journal of Biomolecular NMR.

[6]  B. Meier,et al.  Quantifying proton NMR coherent linewidth in proteins under fast MAS conditions: a second moment approach. , 2019, Physical chemistry chemical physics : PCCP.

[7]  B. Reif,et al.  Determination of methyl order parameters using solid state NMR under off magic angle spinning , 2019, Journal of Biomolecular NMR.

[8]  L. Andreas,et al.  Correcting for magnetic field drift in magic-angle spinning NMR datasets. , 2019, Journal of magnetic resonance.

[9]  B. Reif,et al.  Accurate Determination of 1 H-15 N Dipolar Couplings Using Inaccurate Settings of the Magic Angle in Solid-State NMR Spectroscopy. , 2019, Angewandte Chemie.

[10]  S. Becker,et al.  Alpha protons as NMR probes in deuterated proteins , 2019, Journal of Biomolecular NMR.

[11]  B. Meier,et al.  Spinning faster: protein NMR at MAS frequencies up to 126 kHz , 2019, Journal of Biomolecular NMR.

[12]  Diego F. Gauto,et al.  Microsecond Protein Dynamics from Combined Bloch-McConnell and Near-Rotary-Resonance R1p Relaxation-Dispersion MAS NMR. , 2018, Chemphyschem : a European journal of chemical physics and physical chemistry.

[13]  B. Meier,et al.  Setting the magic angle for fast magic-angle spinning probes. , 2018, Journal of magnetic resonance.

[14]  B. Reif,et al.  Magic-Angle Spinning Frequencies beyond 300 kHz Are Necessary To Yield Maximum Sensitivity in Selectively Methyl Protonated Protein Samples in Solid-State NMR , 2018, The Journal of Physical Chemistry C.

[15]  S. Grzesiek,et al.  Production of isotope-labeled proteins in insect cells for NMR , 2018, Journal of Biomolecular NMR.

[16]  K. Tārs,et al.  Is protein deuteration beneficial for proton detected solid-state NMR at and above 100 kHz magic-angle spinning? , 2017, Solid state nuclear magnetic resonance.

[17]  S. Becker,et al.  Sensory domain contraction in histidine kinase CitA triggers transmembrane signaling in the membrane-bound sensor , 2017, Proceedings of the National Academy of Sciences.

[18]  M. Baldus,et al.  1H‐Detected Solid‐State NMR Studies of Water‐Inaccessible Proteins In Vitro and In Situ , 2016, Angewandte Chemie.

[19]  Y. Nishiyama.  Fast magic-angle sample spinning solid-state NMR at 60-100kHz for natural abundance samples. , 2016, Solid state nuclear magnetic resonance.

[20]  T. Herrmann,et al.  Structure of fully protonated proteins by proton-detected magic-angle spinning NMR , 2016, Proceedings of the National Academy of Sciences.

[21]  Diego F. Gauto,et al.  Sensitive proton-detected solid-state NMR spectroscopy of large proteins with selective CH3 labelling: application to the 50S ribosome subunit. , 2016, Chemical communications.

[22]  L. Tamm,et al.  NMR as a tool to investigate the structure, dynamics and function of membrane proteins , 2016, Nature Structural &Molecular Biology.

[23]  Petra Rovó,et al.  Access to aliphatic protons as reporters in non-deuterated proteins by solid-state NMR. , 2016, Physical chemistry chemical physics : PCCP.

[24]  B. Reif,et al.  Restoring Resolution in Biological Solid-State NMR under Conditions of Off-Magic-Angle Spinning. , 2015, The journal of physical chemistry letters.

[25]  M. Pandey,et al.  Determination of NH proton chemical shift anisotropy with (14)N-(1)H heteronuclear decoupling using ultrafast magic angle spinning solid-state NMR. , 2015, Journal of magnetic resonance.

[26]  K. Houben,et al.  An Efficient Labelling Approach to Harness Backbone and Side-Chain Protons in 1H-Detected Solid-State NMR Spectroscopy , 2015, Angewandte Chemie.

[27]  M. Morris,et al.  Proton-Detected Solid-State NMR Spectroscopy of Bone with Ultrafast Magic Angle Spinning , 2015, Scientific Reports.

[28]  Y. Ishii,et al.  Nano-Mole Scale Side-Chain Signal Assignment by 1H-Detected Protein Solid-State NMR by Ultra-Fast Magic-Angle Spinning and Stereo-Array Isotope Labeling , 2015, PloS one.

[29]  L. Andreas,et al.  High-resolution proton-detected NMR of proteins at very fast MAS. , 2015, Journal of magnetic resonance.

[30]  B. Meier,et al.  Spinning proteins, the faster, the better? , 2015, Journal of magnetic resonance.

[31]  Andrew J. Nieuwkoop,et al.  Sensitivity and resolution of proton detected spectra of a deuterated protein at 40 and 60 kHz magic-angle-spinning , 2015, Journal of biomolecular NMR.

[32]  R. Griffin,et al.  Lipid bilayer-bound conformation of an integral membrane beta barrel protein by multidimensional MAS NMR , 2015, Journal of Biomolecular NMR.

[33]  Oliver F. Lange,et al.  Access to Cα backbone dynamics of biological solids by 13C T1 relaxation and molecular dynamics simulation. , 2015, Journal of the American Chemical Society.

[34]  Woonghee Lee,et al.  NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy , 2014, Bioinform..

[35]  R. Griffin,et al.  Magic Angle Spinning Nuclear Magnetic Resonance Characterization of Voltage-Dependent Anion Channel Gating in Two-Dimensional Lipid Crystalline Bilayers , 2014, Biochemistry.

[36]  B. Meier,et al.  De novo 3D structure determination from sub-milligram protein samples by solid-state 100 kHz MAS NMR spectroscopy. , 2014, Angewandte Chemie.

[37]  Paul Guerry,et al.  Rapid Proton-Detected NMR Assignment for Proteins with Fast Magic Angle Spinning , 2014, Journal of the American Chemical Society.

[38]  Per Larsson,et al.  Structure of the Neisserial Outer Membrane Protein Opa60: Loop Flexibility Essential to Receptor Recognition and Bacterial Engulfment , 2014, Journal of the American Chemical Society.

[39]  A. Goldbourt,et al.  Insights into the spin dynamics of a large anisotropy spin subjected to long-pulse irradiation under a modified REDOR experiment. , 2012, Journal of magnetic resonance.

[40]  N. Dixon,et al.  Backbone assignment of fully protonated solid proteins by 1H detection and ultrafast magic-angle-spinning NMR spectroscopy. , 2012, Angewandte Chemie.

[41]  P. Schanda,et al.  Optimal degree of protonation for 1H detection of aliphatic sites in randomly deuterated proteins as a function of the MAS frequency , 2012, Journal of biomolecular NMR.

[42]  Torsten Herrmann,et al.  Fast resonance assignment and fold determination of human superoxide dismutase by high-resolution proton-detected solid-state MAS NMR spectroscopy. , 2011, Angewandte Chemie.

[43]  A. Gronenborn,et al.  1H-13C/1H-15N heteronuclear dipolar recoupling by R-symmetry sequences under fast magic angle spinning for dynamics analysis of biological and organic solids. , 2011, Journal of the American Chemical Society.

[44]  L. Brown,et al.  Proton-detected solid-state NMR reveals intramembrane polar networks in a seven-helical transmembrane protein proteorhodopsin. , 2011, Journal of the American Chemical Society.

[45]  Lyndon Emsley,et al.  Enhanced Resolution and Coherence Lifetimes in the Solid-State NMR Spectroscopy of Perdeuterated Proteins under Ultrafast Magic-Angle Spinning , 2011 .

[46]  Uwe Fink,et al.  Proton-detected solid-state NMR spectroscopy of fibrillar and membrane proteins. , 2011, Angewandte Chemie.

[47]  Matthias Huber,et al.  A proton-detected 4D solid-state NMR experiment for protein structure determination. , 2011, Chemphyschem : a European journal of chemical physics and physical chemistry.

[48]  U. Fink,et al.  Structure calculation from unambiguous long-range amide and methyl 1H-1H distance restraints for a microcrystalline protein with MAS solid-state NMR spectroscopy. , 2011, Journal of the American Chemical Society.

[49]  P. Schmieder,et al.  High resolution 1H-detected solid-state NMR spectroscopy of protein aliphatic resonances: access to tertiary structure information. , 2010, Journal of the American Chemical Society.

[50]  R. Griffin,et al.  Magic angle spinning NMR investigation of influenza A M2(18-60): support for an allosteric mechanism of inhibition. , 2010, Journal of the American Chemical Society.

[51]  M. Kainosho,et al.  1H-detected 1H-1H correlation spectroscopy of a stereo-array isotope labeled amino acid under fast magic-angle spinning. , 2010, Journal of magnetic resonance.

[52]  I. Ayala,et al.  Stereospecific isotopic labeling of methyl groups for NMR spectroscopic studies of high-molecular-weight proteins. , 2010, Angewandte Chemie.

[53]  L. Emsley,et al.  Dynamics of large nuclear-spin systems from low-order correlations in Liouville space , 2009 .

[54]  B. Reif,et al.  Residual methyl protonation in perdeuterated proteins for multi-dimensional correlation experiments in MAS solid-state NMR spectroscopy. , 2008, Journal of magnetic resonance.

[55]  C. Rienstra,et al.  High-performance solvent suppression for proton detected solid-state NMR. , 2008, Journal of magnetic resonance.

[56]  J. Stewart.  Optimization of parameters for semiempirical methods V: Modification of NDDO approximations and application to 70 elements , 2007, Journal of molecular modeling.

[57]  C. Rienstra,et al.  Proton-detected solid-state NMR spectroscopy of fully protonated proteins at 40 kHz magic-angle spinning. , 2007, Journal of the American Chemical Society.

[58]  J. Griffin,et al.  Residual dipolar couplings by off-magic-angle spinning in solid-state nuclear magnetic resonance spectroscopy. , 2007, Journal of the American Chemical Society.

[59]  I. Kuprov,et al.  Polynomially scaling spin dynamics simulation algorithm based on adaptive state-space restriction. , 2007, Journal of magnetic resonance.

[60]  Steven P. Brown,et al.  Origins of linewidth in H1 magic-angle spinning NMR , 2006 .

[61]  B. Reif,et al.  High resolution 1H detected 1H,13C correlation spectra in MAS solid-state NMR using deuterated proteins with selective 1H,2H isotopic labeling of methyl groups. , 2006, Journal of the American Chemical Society.

[62]  B. Reif,et al.  Ultrahigh resolution in proton solid-state NMR spectroscopy at high levels of deuteration. , 2006, Angewandte Chemie.

[63]  N. Cox,et al.  Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States. , 2006, JAMA.

[64]  W. T. Franks,et al.  Sensitivity and resolution in proton solid-state NMR at intermediate deuteration levels: quantitative linewidth characterization and applications to correlation spectroscopy. , 2006, Journal of magnetic resonance.

[65]  Conrad C. Huang,et al.  UCSF Chimera—A visualization system for exploratory research and analysis , 2004, J. Comput. Chem..

[66]  Kurt W Zilm,et al.  Sensitive high resolution inverse detection NMR spectroscopy of proteins in the solid state. , 2003, Journal of the American Chemical Society.

[67]  M. Hohwy,et al.  1H detection in MAS solid-state NMR spectroscopy of biomacromolecules employing pulsed field gradients for residual solvent suppression. , 2003, Journal of the American Chemical Society.

[68]  T. Meyer,et al.  'Small' talk: Opa proteins as mediators of Neisseria-host-cell communication. , 2003, Current opinion in microbiology.

[69]  M. Bos,et al.  Carcinoembryonic Antigen Family Receptor Recognition by Gonococcal Opa Proteins Requires Distinct Combinations of Hypervariable Opa Protein Domains , 2002, Infection and Immunity.

[70]  Z. Gan,et al.  High-field high-speed MAS resolution enhancement in 1H NMR spectroscopy of solids. , 2001, Solid state nuclear magnetic resonance.

[71]  H. Spiess,et al.  High-resolution 1H NMR spectroscopy in the solid state: very fast sample rotation and multiple-quantum coherences. , 2001, Journal of magnetic resonance.

[72]  R G Griffin,et al.  1H-1H MAS correlation spectroscopy and distance measurements in a deuterated peptide. , 2001, Journal of magnetic resonance.

[73]  Y. Ishii,et al.  Sensitivity enhancement in solid-state (13)C NMR of synthetic polymers and biopolymers by (1)H NMR detection with high-speed magic angle spinning. , 2001, Journal of the American Chemical Society.

[74]  L. Kay,et al.  A robust and cost-effective method for the production of Val, Leu, Ile (δ1) methyl-protonated 15N-, 13C-, 2H-labeled proteins , 1999, Journal of biomolecular NMR.

[75]  M. Achtman,et al.  Sequence Diversity, Predicted Two-Dimensional Protein Structure, and Epitope Mapping of Neisserial Opa Proteins , 1998, Journal of bacteriology.

[76]  L. Kay,et al.  Global folds of highly deuterated, methyl-protonated proteins by multidimensional NMR. , 1997, Biochemistry.

[77]  J. Gauss.  Effects of electron correlation in the calculation of nuclear magnetic resonance chemical shifts , 1993 .

[78]  R. Lamb,et al.  Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block , 1993, Journal of virology.

[79]  Ling Zheng,et al.  Two-dimensional solid-state proton NMR and proton exchange , 1993 .

[80]  A. Becke.  Density-functional thermochemistry. III. The role of exact exchange , 1993 .

[81]  R. Griffin,et al.  High-resolution magic-angle-spinning NMR spectra of protons in deuterated solids , 1992 .

[82]  G. Maciel,et al.  Setting the magic angle using a quadrupolar nuclide , 1982 .

[83]  John S. Waugh,et al.  NMR in rotating solids , 1979 .

[84]  M. Guéron.  Line narrowing and line broadening using trigonometric functions , 1978 .

[85]  O. Jardetzky,et al.  Comparison of convolution and pulse methods for line narrowing in protein NMR spectra , 1978 .

[86]  J. H. Van Vleck,et al.  The Dipolar Broadening of Magnetic Resonance Lines in Crystals , 1948 .

[87]  C. Bewley,et al.  Mammalian expression of isotopically labeled proteins for NMR spectroscopy. , 2012, Advances in experimental medicine and biology.

[88]  J. Klein-Seetharaman,et al.  Isotope labeling in insect cells. , 2012, Methods in molecular biology.

[89]  Hartmut Oschkinat,et al.  Optimum levels of exchangeable protons in perdeuterated proteins for proton detection in MAS solid-state NMR spectroscopy , 2010, Journal of biomolecular NMR.

[90]  R. Tycko,et al.  Measurement of sample temperatures under magic-angle spinning from the chemical shift and spin-lattice relaxation rate of 79Br in KBr powder. , 2009, Journal of magnetic resonance.

[91]  E. Brunner.  Limitations of resolution in the 1H magic angle spinning nuclear magnetic resonance spectroscopy of zeolite. Further results , 1993 .

[92]  E. Brunner.  Limitations of resolution in the 1H magic-angle-spinning nuclear magnetic resonance spectroscopy of zeolites , 1990 .

[93]  G. Bodenhausen,et al.  Principles of nuclear magnetic resonance in one and two dimensions , 1987 .

[94]  G. Bodenhausen,et al.  Natural abundance nitrogen-15 NMR by enhanced heteronuclear spectroscopy , 1980 .