ResearchIntranet
800 MHz Bruker Avance III NMR

Protein NMR Group

Present Research Activities

Our research mainly focuses on the development of multi-dimensional solid-state magic angle spinning NMR techniques for structural and dynamic studies of membrane proteins. For a outline of our major research themes please see the current projects page.

NameRole
Vlad LadizhanskyFaculty
Leonid BrownAssociated Faculty
Seyedmahdi (Mahdi) SadatlavasanibozorgMSc Candidate
Zain Ali *PhD Candidate

* Co-supervised with Leonid Brown

  • Professor Leonid Brown (Physics)
  • Professor Scott D. Ryan (Molecular and Cellular Biology)

Available Positions

We are seeking MSc and PhD students to work in our group. Current projects in the lab focus on understanding of membrane protein folding and protein dynamics; on the role of protein aggregation in Parkinson’s Disease.

We have the equipment and expertise and need your talent and enthusiasm:
If interested, do not hesitate to email Vlad Ladizhansky directly, and inquire about current possibilities.

Content needed

Content needed

Content needed

Protein NMR Projects

Nuclear Magnetic Resonance Spectroscopy - From Nuclear Spin Interactions To Molecular Structure

Our group is interested in the development of solid-state Nuclear Magnetic Resonance (NMR) methods for the characterization of molecular structure, dynamics and interactions at atomic resolution. Our interdisciplinary research spans a wide range of areas from quantum mechanics of spin interactions to practical applications:

  1. Designing new experiments for determination of protein structure. A typical NMR experiment consists of a sequence of radio-frequency pulses, which can be designed to rotate spins and to tailor spin interactions to an optimal form. We are interested in developing new methods for specific experimental needs.
  2. Protein dynamics. In an NMR experiment, nuclear spins are perturbed from equilibrium by radio-frequency pulses; they will eventually come back to equilibrium at a rate that depends on the molecular motions.  From the analysis of nuclear spin relaxation rates one can derive both the time scales and amplitudes of motions. This information is directly related to how molecules function.
  3. Applications of NMR in biophysics and biomedicine. We apply these methods to problems of general biophysical interest, as well as medical/biotechnological relevance, e.g., design of new pharmacological drugs, understanding of the molecular origins of diseases, etc.

Representative publications

  1. S. Wang et al. Solid-state NMR spectroscopy structure determination of a lipid-embedded heptahelical membrane protein. Nature Methods (2013), 10, 107.
  2. D. Good et al. Solid-state NMR provides evidence for small-amplitude slow domain motions in a multi-spanning transmembrane α–helical protein,  J. Am. Chem. Soc. (2017), 139, 9246. 
  3. P. Xiao et al. Solid-state NMR spectroscopy based atomistic view of a membrane protein unfolding pathway. Nature Commun (2019), 10, 3867.
     
Bruker Dynamic Nuclear Polarization Spectrometer

Equipment

Our group is well equipped, and has access to various Bruker instruments 500 MHz, 600 MHz, and 800 MHz proton frequencies, and the only in Canada Dynamic Nuclear Polarization spectrometer. All spectrometers are equipped with state of the art solid-state and solution NMR probes. We also enjoy and benefit from collaboration with Bruker Canada and Bruker USA. For more details see visit the NMR Centre.

Publications

  • Partial magic angle spinning NMR 1H, 13C, 15N resonance assignments of the flexible regions of a monomeric alpha-synuclein: conformation of C-terminus in the lipid-bound and amyloid fibril states. J. Medeiros, V. V. Bamm, C. Jany, C. Coackley, M. E. Ward, G. Harauz, S.D. Ryan V. Ladizhansky. Biomol NMR Assign 15, 297–303 (2021)
  • Identifying lipids tightly bound to an integral membrane protein. JE de Vlugt, P Xiao, R Munro, A Charchoglyan, D Brewer,  S. Al-Abdul-Wahid, L. S Brown, V. Ladizhansky. Biochimica et Biophysica Acta (BBA)-Biomembranes 1862, 183345 (2020)
  • Improved protocol for the production of the low-expression eukaryotic membrane protein human aquaporin 2 in Pichia pastoris for solid-state NMR.RA Munro, J de Vlugt, V Ladizhansky, LS Brown. Biomolecules 10, 434 (2020)
  • Solid-state NMR spectroscopy based atomistic view of a membrane protein unfolding pathway. P Xiao, D Bolton, RA Munro, LS Brown, V Ladizhansky. Nature communications 10, 1-11 (2019)
  • Structure of the functionally important extracellular loop C of human aquaporin 1 obtained by solid-state NMR under nearly physiological conditions. DA Dingwell, LS Brown, V Ladizhansky. The Journal of Physical Chemistry B 123, 7700-7710 (2019)
  • Biosynthetic production of fully carbon-13 labeled retinal in E. coli for structural and functional studies of rhodopsins. RA Munro, J de Vlugt, ME Ward, SY Kim, KA Lee, KH Jung, V. Ladizhansky, L.S. Brown. Journal of Biomolecular NMR 73, 49-58 (2019)
  • A biradical-tagged phospholipid as a polarizing agent for solid-state MAS Dynamic Nuclear Polarization NMR of membrane proteins. DB Good, MA Voinov, D Bolton, ME Ward, IV Sergeyev, M Caporini, P. P Scheffer, A Lo, M Rosay, A Marek, LS Brown, AI Smirnov, V.L Ladizhansky. Solid State Nuclear Magnetic Resonance 100, 92-101 (2019)
  • Partial solid-state NMR 1 H, 13 C, 15 N resonance assignments of a perdeuterated back-exchanged seven-transmembrane helical protein Anabaena Sensory Rhodopsin. D Bolton, LS Brown, V Ladizhansky. Biomol. NMR Assign. 12, 237-242 (2018)
  • V. Ladizhansky, 2017. Applications of solid-state NMR to membrane proteins. DOI: 10.1016/j.bbapap.2017.07.004.
     
  • D. Good, C. Pham, J. Jagas, J.R. Lewandowski, V. Ladizhansky, 2017. Solid-State NMR Provides Evidence for Small-Amplitude Slow Domain Motions in a Multispanning Transmembrane α-Helical Protein. J. Am. Chem. Soc., 139, 9246.
     
  • S. Milikisiyants, S. Wang, R.A. Munro, M. Donohue, M.E. Ward, D. Bolton, L.S. Brown, T.I. Smirnova, V. Ladizhansky, A.I. Smirnov, 2017. Oligomeric Structure of Anabaena Sensory Rhodopsin in a Lipid Bilayer Environment by Combining Solid-State NMR and Long-range DEER Constraints. J. Mol. Biol., 429, 1903.
     
  • S. Wang, C. Ing, S. Emami, Y. Jiang, H. Liang, R. Pomès, L.S. Brown, V. Ladizhansky. 2016. Structure and Dynamics of Extracellular Loops in Human Aquaporin-1 from Solid-State NMR and Molecular Dynamics. J. Phys. Chem. B. 120, 9887.
     
  • M.A. Rogers, Q. Feng, V. Ladizhansky, D.B. Good, A.K. Smith, M. Corridini, D.A.S. Grahame, B.C. Bryksa, P.D. Jadhav, S. Sammynaiken, L.-T. Lim, B. Guild, Y.Y. Shim, P.-G. Burnett, M.J.T. Reaney, 2016. Self-assembled fibrillar networks comprised of a naturally-occurring cyclic peptide—LOB3. RSC Advances 6, 40765.
     
  • M.E. Ward, E. Ritz, M.A. Ahmed, V.V. Bamm, G. Harauz, L.S. Brown, V. Ladizhansky, 2015. Proton detection for signal enhancement in solid-state NMR experiments on mobile species in membrane proteins. J. Biomol. NMR 63, 375.
     
  • M.A. Voinov, D.B. Good, M.E. Ward, S. Milikisiyants, A. Marek, M.A. Caporini, M. Rosay, R.A. Munro, M. Ljumovic, L.S. Brown, V. Ladizhansky, A.I. Smirnov, 2015. Cysteine-Specific Labeling of Proteins with a Nitroxide Biradical for Dynamic Nuclear Polarization NMR. J. Phys. Chem. B. 119, 10180.
     
  • L.S. Brown, V. Ladizhansky, 2015. Membrane proteins in their native habitat as seen by solid-state NMR spectroscopy. Prot. Sci. 24, 1333. Editors Highlights
     
  • M.E. Ward, S. Wang, R. Munro, E. Ritz, I. Hung, P.L. Gor'kov, Y. Jiang, H. Liang, L.S. Brown, V. Ladizhansky, 2015. In situ structural studies of Anabaena sensory rhodopsin in the E. coli membrane. Biophys J. 108, 1683. Article featured as New and Notable 
     
  • M.E. Ward, L.S. Brown, V. Ladizhansky, 2015. Advanced solid-state NMR techniques for characterization of membrane protein structure and dynamics: application to Anabaena Sensory Rhodopsin. J. Magn. Reson. 253, 119.
     
  • S. Wang,V. Ladizhansky, 2014. Recent advances in magic angle spinning solid state NMR of membrane proteins. Prog. Nucl. Magn. Reson. Spectrosc. 82, 1.
     
  • V. Ladizhansky, 2014. Recent advances in magic angle spinning solid-state NMR of proteins. Isr. J. Chem. 54, 866 
     
  • D.B. Good, S. Wang, M.E. Ward, J. O. Stuppe, L.S. Brown, J. Lewandowski, V. Ladizhansky. 2014. Conformational dynamics of a seven transmembrane helical protein Anabaena Sensory Rhodopsin probed by solid-state NMR. J. Am. Chem. Soc. 36, 2833. Article selected for JACS Spotlights 
     
  • L. Kuang, D.A. Fernandes, M. O'Halloran, W. Zheng, Y. Jiang, V. Ladizhansky, L.S. Brown, H. Liang, 2014. "Frozen" Block Copolymer Nanomembranes with Light-Driven Proton Pumping Performance.ACS Nano, 28, 537. 
     
  • M.E.Ward, S. Wang, S. Krishnamurthy, H. Hutchins, M. Fey, L.S. Brown, V. Ladizhansky, 2014. High-resolution paramagnetically enhanced solid-state NMR spectroscopy of membrane proteins at fast magic angle spinning. J. Biomol. NMR, 58, 37. 
     
  • G.T. Debelouchina, M.J. Bayro, A.W. Fitzpatrick, V. Ladizhansky, M.T. Colvin, M.A. Caporini, C.P. Jaroniec, V.S. Bajaj, M. Rosay, C.E. Macphee,M. Vendruscolo, W.E. Maas, C.M. Dobson, R.G. Griffin, 2013 .Higher Order Amyloid Fibril Structure by MAS NMR and DNP Spectroscopy. J. Am. Chem. Soc, 135, 19237.
     
  • S. Wang, R.A. Munro, L. Shi, I. Kawamura, T. Okitsu, A. Wada, S.Y. Kim, K.H. Jung, L.S. Brown, V. Ladizhansky, 2013. Solid-state NMR spectroscopy structure determination of a lipid-embedded heptahelical membrane protein. Nature Methods, 10, 1007. 
     
  • A.W. Fitzpatrick, G.T. Debelouchina, M.J. Bayro, D.K. Clare, M.A. Caporini, V.S. Bajaj, C.P. Jaroniec, L. Wang, V. Ladizhansky, S.A. MN|ller, C.E. MacPhee, C.A. Waudby, H.R. Mott, A. De Simone,T.P. Knowles, H.R. Saibil,M. Vendruscolo, E.V. Orlova, R.G. Griffin, C.M. Dobson, 2013. Atomic structure and hierarchical assembly of a cross-beta amyloid fibril. Proc Natl Acad Sci U S A., 110, 5468.
     
  • S. Emami, Y. Fan, R. Munro, V. Ladizhansky, L.S. Brown, 2013. Yeast-expressed human membrane protein aquaporin-1 yields excellent resolution of solid-state MAS NMR spectra. J Biomol NMR. 55, 147.
     
  • S. Wang, R.A. Munro, S.Y. Kim, K.H. Jung, L.S. Brown, V. Ladizhansky, 2012. Paramagnetic relaxation enhancement reveals oligomerization interface of a membrane protein. J Am Chem Soc. 2012, 134, 16995.
     
  • S. Wang, L. Shi, T. Okitsu, A. Wada, L.S. Brown, V. Ladizhansky, 2013. Solid-state NMR (13)C and (15)N resonance assignments of a seven-transmembrane helical protein Anabaena Sensory Rhodopsin. Biomol NMR Assign, 7, 253. 
     
  • L. Shi, V. Ladizhansky, 2012. Magic angle spinning solid-state NMR experiments for structural characterization of proteins. Methods Mol Biol. 895, 153. 
     
  • M.E. Ward, L. Shi, E.M. Lake, S.Krishnamurthy,H. Hutchins, L.S. Brown, V. Ladizhansky, 2011. Proton Detected Solid-State NMR Reveals Intramembrane Polar Networks in a Seven-Helical Transmembrane Protein Proteorhodopsin. J. Am. Chem. Soc., 133, 17434-17443 
     
  • S. Wang, L. Shi, I. Kawamura, L.S. Brown, V. Ladizhansky, 2011. Site-Specific Solid-State NMR Detection of Hydrogen-Deuterium Exchange Reveals Conformational Changes in a 7-Helical Transmembrane Protein. Biophys. J, 101, L23-L25. 
     
  • S. Wang, S.Y. Kim, K.-H. Jung, V. Ladizhansky, L.S. Brown, 2011. A Eukaryotic-Like Interaction of Suluble Cyanobacterial Sensory Rhodopsin Transducer with DNA. J. Mol. Biol., 411, 449-462.
     
  • L. Shi, I. Kawamura, K.-H. Jung, L. S. Brown, V. Ladizhansky, 2011. Molecular conformation of a seven-helical transmembrane photosensor in the lipid environment. Angew. Chemie Int. Ed., 50, 1302-1305 .
     
  • Y. Fan, L. Shi, V. Ladizhansky, L.S. Brown, 2011. Uniform isotope labeling of a eukaryotic seven-transmembrane helical protein in yeast enables high-resolution solid-state NMR studies in the lipid environment. J Biomol NMR, 49, 151-161.
     
  • M.A. Ahmed, V.V. Bamm, G. Harauz, V. Ladizhansky, 2010. Solid-state NMR spectroscopy of membrane-associated myelin basic protein-conformation and dynamics of an immunodominant epitope, Biophys J. 99, 1247-1255. 
     
  • L. Shi, E. Lake, M. Ahmed, L.S. Brown and V. Ladizhansky, 2009. Solid-state NMR study of proteorhodopsin in the lipid environment: secondary structure and dynamics. BBA-Biomembranes, 1788, 2563-2574 
     
  • V. Ladizhansky, 2009. Homonuclear dipolar recoupling techniques for structure determination in uniformly 13C-labeled proteins. Solid State Nucl. Magn. Reson., 36, 119-28.
     
  • L. Shi, M. A. Ahmed, G. Whited, W. Zhang, L. S. Brown, V. Ladizhansky, 2009. "Three-dimensional solid-state NMR study of seven-helical integral membrane proton pump: partial spectral assignments and structural insights", J. Mol. Biol. 386, 1078-1093.
     
  • M. A. Ahmed, V. V. Bamm, L. Shi, M. Steiner-Mosonyi, J. F. Dawson, L.S. Brown, G. Harauz, V. Ladizhansky, 2009. "Induced secondary structure and polymorphism in an intrinsically disordered structural linker of the CNS - Solid-state NMR and FTIR spectroscopy of 18.5 kDa myelin basic protein bound to actin", Biophys. J., 96, 180-191.
     
  • L. Shi, X. Peng, M.A. Ahmed, D. Edwards, L.S. Brown, V. Ladizhansky, 2008. "Resolution enhancement by homonuclear J-decoupling: application to three-dimensional solid-state magic angle spinning NMR spectroscopy". J Biomol. NMR, 41, 9-15.
     
  • X. Peng, D. Libich, R. Janik, G. Harauz, and V. Ladizhansky, 2008. "Dipolar Chemical Shift Correlation Spectroscopy for Homonuclear Carbon Distance Measurements in Proteins in the Solid State: Application to Structure Determination and Refinement", J. Am. Chem. Soc., 130, 359-369.
     
  • G. Harauz, V. Ladizhansky, 2008. "Structure and dynamics of the myelin basic protein (MBP) family by solution and solid-state NMR". Chapter X (pp 196-231) in Joan M. Boggs (editor),"Myelin Basic Protein", Series on "Intrinsically Disordered Proteins" (edited by Vladimir Uversky). Nova Science Publishers.
     
  • L. Zhong, V. Bamm, M.A. Ahmed, G. Harauz, and V. Ladizhansky, 2007. "Solid-state NMR spectroscopy of 18.5 kDa myelin basic protein reconstituted with lipid vesicles: spectroscopic characterisation and spectral assignments of solvent-exposed protein fragments", BBA-Biomembranes, 1768, 3193-3205.

Alumni

  • Dr. Lichi Shi
  • Dr. Shenlin Wang

  • Dr. Izuru Kawamura
  • Dr. Hailiang Zhou

  • Daryl Good
  • Meaghan Ward
  • Sanaz Emami
  • Lichi Shi 
  • Mumdooh Ahmed

  • Raoul Vaz
  • Justin Medeiros
  • Rachel Brown
  • David Bolton
  • Jeff de Vlugt
  • Hansul (David) Park
  • Ligang Zhong
  • Xiaohu Peng
  • Rafal Janik
  • Andrew Gravelle
  • Emily Ritz
  • Lichi Shi 

  • Eve Lake
  • Jake Jagas

Contact

Department of Physics, Main Office
MacNaughton Building, Room 207
1-519-824-4120 x 52261

Courier to:
488 Gordon Street
Physics, Science Complex, Rm 1110
Guelph, ON | N1G 2W1

Department Links

Socials

 Instagram

 YouTube

 Twitter

 Facebook