• Andrew J. Nieuwkoop
  • Assistant Professor
  • Research Synopsis: Magic angle spinning solid-state NMR of proteins, membranes, and materials.
  • Phone: (848) 445-2626




The Nieuwkoop lab focuses on using magic-angle-spinning solid-state NMR (ssNMR) to address challenging areas of structural biology. We focus on methods development, especially through very fast spinning, to access samples that would otherwise be hard to investigate. In particular, the lab focuses on 1H-detection, which is becoming more and more powerful as the spinning possible available increase. We seek to investigate the structure and dynamics of lipids and the membranes they form, in order to better understand their function. In addition, we study membrane proteins, whose activity depends upon interactions with lipid bilayers, for which ssNMR is a great tool for atomic resolution investigations.

Lipids and Membranes

Lipid bilayers are a key component of a cell. In addition to providing a barrier, they control the activity of a vast array of proteins and are used to transmit molecules and signals within and outside of the cell. The atomic details of how these signals and interactions take place can be investigated via ssNMR. We seek to understand how subtle differences in lipid head-groups and dynamics have dramatic effects on the properties fo the bilayer and the specific interactions with proteins.

Membrane proteins

Membrane proteins make up a large and understudied portion of the human genome. Because of the challenges of studying them in their native lipid environment, much of what we know about their structure and function comes from samples in detergent or bilayer mimetics. However, we know that the exact composition of the membrane can have large effects on the activity of membrane proteins. Therefore, we are developing methods to investigate membrane proteins in native or near-native environments. This includes assignment and structure determination, as well as site-specific protein lipid interactions.

1H Detection methods

We seek to apply the power of 1H-detected ssNMR to growing numbers of areas in ssNMR. Due to the fact 1H’s gyromagnetic ratio is 4 times that of 13C, experiments detecting 1H are more sensitive and therefore faster. While 1H detection is increasing well developed in terms of chemical shift assignments, there is still a wide array of areas where it has not yet been deployed. We are developing new pulse sequences to determine intermolecular distances both within a protein and intermolecularly, as well as study dynamics at many timescales.

All Publications 


Selected Publications 

  • Hernando, M.; Orriss, G.; Perodeau, J.; Lei, S.; Ferens, F. G.; Patel, T. R.; Stetefeld, J.; Nieuwkoop, A. J.; O'Neil, J. D., Solution structure and oligomeric state of the E. coliglycerol facilitator. Biochim. Biophys. Acta, Biomembr. 2020, 1862 (5), 183191. (http://doi.org/10.1016/j.bbamem.2020.183191)

  • Friedrich, D.; Perodeau, J.; Nieuwkoop, A. J.; Oschkinat, H., MAS NMR detection of hydrogen bonds for protein secondary structure characterization. J. Biomol. NMR 2020, 74 (4-5), 247-256. (http://doi.org/10.1007/s10858-020-00307-z)

  • Retel, J. S., Nieuwkoop, A. J., Hiller, M., Higman, V. A., Barbet-Massin, E., Stanek, J., Andreas, L. B., Franks, W. T., VanRossum, B., Vinothkumar, K. R., Handel, L., Giuseppe-Palma, G., Bardiaux, B., Pintacuda, G., Emsley, L., Kühlbrandt, W., Oschkinat, H. “Structure of Outer Membrane Protein G in Lipid Bilayers” Nat. Comm. 2017 8(1), 2073. (http://doi.org/10.1038/s41467-017-02228-2)

  • Tuttle, M. D., Comellas, G., Nieuwkoop, A. J., Covell, D. J., Berthold, D. A., Kloepper, K. D., Courtney, J. M., Kim, J. K., Barclay, A. M., Kendall, A., Wan, W., Stubbs, G., Schwieters, C. D., Lee, V. M. Y., George, J. M. and Rienstra, C. M. "Solid-state NMR structure of a pathogenic fibril of full-length human alpha-synuclein" Nat. Struct. Mol. Biol. 2016 23(5), 409-15. (http://doi.org/10.1038/nsmb.3194)

  • Nieuwkoop, A. J., Franks, W. T., Rehbein, K., Diehl, A., Akbey, U., Engelke, F., Emsley, L., Pintacuda, G. and Oschkinat, H. "Sensitivity and resolution of proton detected spectra of a deuterated protein at 40 and 60 kHz magic-angle-spinning" J. Biomol. NMR. 2015 61(2), 161-71. (http://doi.org/10.1007/s10858-015-9904-0)

  • Barbet-Massin, E., Pell, A. J., Retel, J. S., Andreas, L. B., Jaudzems, K., Franks, W. T., Nieuwkoop, A. J., Hiller, M., Higman, V., Guerry, P., Bertarello, A., Knight, M. J., Felletti, M., Le Marchand, T., Kotelovica, S., Akopjana, I., Tars, K., Stoppini, M., Bellotti, V., Bolognesi, M., Ricagno, S., Chou, J. J., Griffin, R. G., Oschkinat, H., Lesage, A., Emsley, L., Herrmann, T. and Pintacuda, G. "Rapid proton-detected NMR assignment for proteins with fast magic angle spinning" J. Am. Chem. Soc. 2014 136(35), 12489-97. (http://doi.org/10.1021/ja507382j)

  • Anderson, T. M., Clay, M. C., Cioffi, A. G., Diaz, K. A., Hisao, G. S., Tuttle, M. D., Nieuwkoop, A. J., Comellas, G., Maryum, N., Wang, S., Uno, B. E., Wildeman, E. L., Gonen, T., Rienstra, C. M. and Burke, M. D. "Amphotericin forms an extramembranous and fungicidal sterol sponge" Nat. Chem. Biol. 2014 10(5), 400-6. (http://doi.org/10.1038/nchembio.1496)

  • Zhou, D. H., Nieuwkoop, A. J., Berthold, D. A., Comellas, G., Sperling, L. J., Tang, M., Shah, G. J., Brea, E. J., Lemkau, L. R. and Rienstra, C. M. "Solid-state NMR analysis of membrane proteins and protein aggregates by proton detected spectroscopy" J. Biomol. NMR. 2012 54(3), 291-305. (http://doi.org/10.1007/s10858-012-9672-z)

  • Nieuwkoop, A. J. and Rienstra, C. M. "Supramolecular protein structure determination by site-specific long-range intermolecular solid state NMR spectroscopy" J. Am. Chem. Soc. 2010 132(22), 7570-1. (http://doi.org/10.1021/ja100992y)

  • Nieuwkoop, A. J., Wylie, B. J., Franks, W. T., Shah, G. J. and Rienstra, C. M. "Atomic resolution protein structure determination by three-dimensional transferred echo double resonance solid-state nuclear magnetic resonance spectroscopy" J. Chem. Phys. 2009 131(9), 095101. (http://doi.org/10.1063/1.3211103)

  • Franks, W. T., Wylie, B. J., Schmidt, H. L., Nieuwkoop, A. J., Mayrhofer, R. M., Shah, G. J., Graesser, D. T. and Rienstra, C. M. "Dipole tensor-based atomic-resolution structure determination of a nanocrystalline protein by solid-state NMR" Proc. Natl. Acad. Sci. U. S. A. 2008 105(12), 4621-6. (http://doi.org/10.1073/pnas.0712393105)

  • Zhou, D. H., Shea, J. J., Nieuwkoop, A. J., Franks, W. T., Wylie, B. J., Mullen, C., Sandoz, D. and Rienstra, C. M. "Solid-state protein-structure determination with proton-detected triple-resonance 3D magic-angle-spinning NMR spectroscopy" Angew Chem Int Ed Engl. 2007 46(44), 8380-3. (http://doi.org/10.1002/anie.200702905)

People Page