The overall goal of the research is to develop solid-state NMR spectroscopy so that it can be used to determine the structures of peptides and proteins in the crystalline solid-state and in membrane bilayers. Synthetic peptides with well-defined structural features and isotopic labels at specific locations will continue to play crucial roles in the development of all new spectroscopic methods. Sample orientation and magic angle sample spinning have different but equally dramatic effects on the spectra. In an oriented sample, a resonance can occur at any frequency within the span of the powder pattern. In the case of magic angle sample spinning, each resonance occurs at its isotropic frequency. We will develop and apply both types of solid-state NMR experiments to peptides, globular proteins, and membrane proteins. Oriented sample solid-state NMR experiments will be improved through the use of a very high field magnet and low sample temperatures. Multidimensional triple-resonance experiments suitable for application to uniformly 13C and 15N labeled proteins will continue to be developed. 1H, 13C, and 15N chemical shift tensors in backbone and side chain sites of peptides will be determined on polycrystalline samples using a three-dimensional correlation experiment; these results will provide essential information for the interpretation of both solution NMR and solid-state NMR experimental results. Having determined the structure of the M2 channel-forming peptide from the Acetylcholine receptor in lipid bilayers, we will utilize the methods of oriented sample NMR to determine the structures of polypeptides that constitute a functional voltage-gated ion channel. Encouraged by recent results obtained with very high-speed sample spinning, we will apply magic angle sample spinning solid-state NMR experiments to peptides and proteins. In particular, we will compare the results obtained from a 79- residue globular protein to those from an 80-residue membrane protein.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Biophysical Chemistry Study Section (BBCB)
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Wehrle, Janna P
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University of California San Diego
Schools of Arts and Sciences
La Jolla
United States
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Park, Sang Ho; Das, Bibhuti B; De Angelis, Anna A et al. (2010) Mechanically, magnetically, and ""rotationally aligned"" membrane proteins in phospholipid bilayers give equivalent angular constraints for NMR structure determination. J Phys Chem B 114:13995-4003
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Nevzorov, Alexander A; Opella, Stanley J (2003) Structural fitting of PISEMA spectra of aligned proteins. J Magn Reson 160:33-9
Mesleh, M F; Valentine, K G; Opella, S J et al. (2003) Myristoylation as a general method for immobilization and alignment of soluble proteins for solid-state NMR structural studies. J Biomol NMR 25:55-61
Nevzorov, Alexander A; Opella, Stanley J (2003) A ""magic sandwich"" pulse sequence with reduced offset dependence for high-resolution separated local field spectroscopy. J Magn Reson 164:182-6
Mesleh, Michael F; Lee, Sangwon; Veglia, Gianluigi et al. (2003) Dipolar waves map the structure and topology of helices in membrane proteins. J Am Chem Soc 125:8928-35
Zeri, Ana Carolina; Mesleh, Michael F; Nevzorov, Alexander A et al. (2003) Structure of the coat protein in fd filamentous bacteriophage particles determined by solid-state NMR spectroscopy. Proc Natl Acad Sci U S A 100:6458-63
Lee, Sangwon; Mesleh, Michael F; Opella, Stanley J (2003) Structure and dynamics of a membrane protein in micelles from three solution NMR experiments. J Biomol NMR 26:327-34
Mesleh, Michael F; Opella, Stanley J (2003) Dipolar Waves as NMR maps of helices in proteins. J Magn Reson 163:288-99

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