Dr. Benjamin J. Wylie
Title: Assistant Professor
Education: Ph.D., University of Illinois Urbana-Champaign
Postdoctoral Fellow, Columbia University
Research Area: Biochemisty /Physical Chemistry
Office: Chemistry 034
Principal Research Interests
- Solid-State NMR
- Structural Biology
- Membrane Proteins
Professor Wylie's research interests involve using state of the art solid-state nuclear magnetic resonance (SSNMR) to study the structure and function of membrane proteins. Specifically, research in the Wylie laboratory will expand our understanding of the structure and function of transmembrane K+ channels and receptors in lipid bilayers and native membranes.
K+ channels are the most numerous type of ion channel across all species; they regulate action and resting membrane potentials, and are important drug targets. We seek to elucidate the structural changes and intermediate states associated with K+ channel opening and inactivation in lipid bilayers. The next step will be to characterize the structural and membrane perturbations introduced by channel binding toxins from animal venoms.
G protein coupled receptors (GPCRs) comprise a large super-family of proteins sharing a 7TM helical fold and are targeted by nearly half of existing pharmaceuticals. Active GPCRs will be studied in bilayer environments. Site-specific chemical shifts of active GPCRs will be assigned and used to map structural changes upon activation and deactivation in response to native or synthetic ligands. Further experiments will be designed to identify micro- switches and the role of both lipids and water in receptor function and activation.
SSNMR is a kind of NMR spectroscopy used to study the structure and dynamics of samples that lack isotropic mobility. These systems include integral membrane proteins and fibrillar aggregates that are essential for cell function or are implicated in multiple human diseases. Membrane proteins comprise a third of known proteins in most genomes, and are essential to many critical functions such as ion conduction, energy transduction, and signaling across the membrane. Unfortunately, few structures of these systems are known. The flexibility of SSNMR allows membrane protein samples to be prepared in local environments ranging from detergents, to liposomes, to native membranes. SSNMR may even provide novel structural and functional information for proteins with a known structure from x-ray crystallography because samples can be prepared under conditions closer to those observed in vivo.
- Wylie, B. J.; Bhate, M.P.; McDermott, A. E. (2014) "Transmembrane allosteric coupling of the gates in a potassium channel."Proceedings of the National Academy of Sciences U.S.A. 111 (1) pp. 185-190.
- Wylie, B. J.; Sperling, L. J.; Nieuwkoop, A. J.; Franks, W. T.; Oldfield, E.; Rienstra, C. M. (2011) "Ultra-high resolution protein structures using NMR chemical shift tensors."Proceedings of the National Academy of Sciences U.S.A. 108 (41) pp. 16974-16979.
- Bhate, M. P.; Wylie, B. J.; Tian, L.; McDermott, A. E. (2010) "Conformational dynamics in the selectivity filter of KcsA in response to potassium ion concentration." Journal of Molecular Biology 401 (2) pp. 155-166.
- Nieukoop, A. J.; Wylie, B. J.; Franks, W. T.; Rienstra, C. M. (2009) "Atomic resolution protein structure determination by three-dimensional transferred echo double resonance solid-state nuclear magnetic resonance spectroscopy."J. Chem. Phys. 131:095101.
- Wylie, B. J.; Schwieters, C. D.; Oldfield, E.; Rienstra, C. M. (2009) "Protein structure refinement using 13Ca chemical shift tensors."Journal of the American Chemical Society 131 (3) pp. 985-992.
- Franks, W. T.; Wylie, B. J.; Frericks-Schmidt, H. L; Nieuwkoop, A. J.; Mayrhofer, R. M.; Shah, G. J.; Graesser, D. T.; Rienstra, C. M. (2008) "Dipole tensor-based refinement for atomic-resolution structure determination of a nanocrystalline protein by solid-state NMR spectroscopy."Proceedings of the National Academy of Sciences U.S.A. 105 (12) pp. 4621-4626.
- Wylie, B. J.; Sperling, L. J.; Rienstra, C. M. (2008) "Isotropic chemical shifts in magic-angle spinning NMR spectra of proteins."Physical Chemistry Chemical Physics 10 (3) pp. 405-413.
- Wylie, B. J.; Sperling, L. J.; Frericks, H. L.; Shah, G. A.; Franks, W. T.; Rienstra, C. M. (2007) "Chemical-shift anisotropy measurements of amide and carbonyl resonances in a microcrystalline protein with slow magic-angle spinning NMR spectroscopy."Journal of the American Chemical Society 129 (17) pp. 5318-5319.
- Wylie, B. J.; Franks, W. T.; Rienstra, C. M. (2006) "Determinations of 15N chemical shift anisotropy magnitudes in a uniformly-15N,13C-labeled microcrystalline protein by 3D magic-angle spinning NMR spectroscopy." Journal of Physical Chemistry B 110 (22) pp. 10926-10936.
- Wylie, B. J.; Franks, W. T.; Graesser, D. T.; Rienstra, C. M. (2005) "Site-specific 13C chemical shift anisotropy measurements in a uniformly-15N,13C-labeled microcrystalline protein by 3D magic-angle spinning NMR spectroscopy."Journal of the American Chemical Society 127 (34) pp. 11946-11947.
Department of Chemistry & Biochemistry
Address1204 Boston Avenue, Lubbock, TX 79409-1061
Phone806.742.3067 | Fax: 806.742.1289