My research focuses on the development of solid-state NMR methodology and applications of solution and solid-state NMR to study relationships between structure, dynamics and activity of biomolecular systems. I am particularly interested in atomic resolution characterization of solid and solid-liquid interface biological systems including, but not limited to, protein complexes, amyloid fibrils, and membrane proteins. Because the line widths in the NMR spectra in the solid state do not depend on the size of molecule as they do in solution, solid-state NMR offers unique opportunities to study structure and dynamics of proteins as a part of even very large assemblies. Importantly, solid-state NMR methodology can be applied to soluble and crystallisable systems but also to systems that are not soluble or that cannot be crystallised. Membrane proteins perform crucial functions such as signaling and transport of materials across membrane. Amyloid fibrils, a primer in self-assembling systems, are probably best known for their implication in debilitating neurodegenerative diseases such as Alzheimer’s or Parkinson’s. However, they are also involved in normal physiological processes such as biosynthesis of melanin. Understandably, both membrane proteins and amyloid fibrils captivate not only for their intriguing biophysics, but also for their medical relevance, e.g. over 50% of all drug targets act on membrane–bound receptors. However, they often lack long-range crystallinity and are insoluble and therefore, not easily amenable to detailed structural characterization by the traditional biophysical methods such as single-crystal x-ray crystallography and solution NMR. At the same, often even in the absence of long-range order they exhibit sufficient local order to allow for detailed atomic resolution description of both structure and dynamics by solid-state NMR.
Direct observation of hierarchical protein dynamics, Lewandowski, J.R., Halse, M.E., Blackledge, M., Emsley, L. Science 2015 348 (6234): 578-581. Link: http://www.sciencemag.org/content/348/6234/578
Intermolecular interactions and protein dynamics by SSNMR Lamley, J.M., Öster, C., Stevens, R.A., Lewandowski, J.R. Angewandte Chemie 2015 54(51), 15374–15378. DOI: 10.1002/anie.201509168
Unraveling the complexity of protein backbone dynamics with combined 13C and 15N solid-state NMR relaxation measurements Lamley, J. M.; Lougher, M. J.; Sass, H. J.; Rogowski, M.; Grzesiek, S.; Lewandowski, J. R. Phys. Chem. Chem. Phys. 2015, 17 (34), 21997.
Solid-State NMR of a Protein in a Precipitated Complex with a Full-Length Antibody, Lamley, J.M., Iuga, D., Öster, C., Sass, H.J., Rogowski, M., Oss, A., Past, J., Reinhold, A., Grzesiek, S., Samoson, A., Lewandowski, J.R. J. Am. Chem. Soc. 2014 136 (48):16800–16806. Link: http://pubs.acs.org/doi/abs/10.1021/ja5069992 (Open Access)
Conformational dynamics of a seven transmebrane helical protein Anabaena Sensory Rhodopsin probed by solid-state NMR. Good, DB, Wang, S, Ward, ME, Struppe, JO, Brown, LS, Lewandowski, JR, Ladizhansky, V J. Am. Chem. Soc. 2014 136, 2833–2842. DOI: 10.1021/ja411633w
Site-specific Measurement of Slow Motions in Proteins. Lewandowski JR, Sass HJ, Grzesiek S, Blackledge M, Emsley J. Am. Chem. Soc. 2011 133:16762-16765. doi://10.1021/ja206815h
Structural Complexity of a Composite Amyloid Fibril Lewandowski JR, van der Wel PC a, Rigney M, Grigorieff N, Griffin RG J. Am. Chem. Soc. 2011 133: 9457-9469. doi://10.1021/ja203736z
Measurement of site-specific 13C spin-lattice relaxation in a crystalline protein Lewandowski JR, Sein J, Sass HJ, Grzesiek S, Blackledge M, Emsley L J. Am. Chem. Soc. 2010 132:8252-4. doi://10.1021/ja102744b
High-resolution solid-state NMR structure of a 17.6 kDa protein Bertini I, Bhaumik A, De Paëpe G, Griffin RG, Lelli M, Lewandowski JR, Luchinat C J. Am. Chem. Soc. 2010 132:1032-40. doi://10.1021/ja906426p
Proton assisted recoupling and protein structure determination De Paëpe G, Lewandowski JR, Loquet A, Böckmann A, Griffin RG J. Chem. Phys. 2008 129:245101. doi://10.1063/1.3036928
Proton assisted insensitive nuclei cross polarization Lewandowski JR, De Paëpe G, Griffin RG J. Am. Chem. Soc. 2007 129:728-9. doi://10.1021/ja0650394