Separovic Research Group

NMR and Membrane Biophysics

Structure of Membrane-Active Peptides

FS_2014Advancements in bio/nano-technology require insights from studies of biology at the molecular level. We, Separovic Lab @ Bio21, study the biophysical chemistry of membrane-active peptides and proteins relevant to disease states and treatments.

The structure-function relationships of macromolecular assemblies at the atomistic level are examined through the use of powerful solid-state nuclear magnetic resonance (NMR) methods to determine the structure and dynamics of crystalline/amorphous powders, protein complexes and biological membranes.

NMR spectroscopy, complemented by a range of biophysical techniques, is being used to determine the mechanism of action of membrane polypeptides. Our primary goal is to do this for membrane components in situ. We have determined the 3D structure of peptides, the antibiotic gramicidin A and the bee toxin melittin, in phospholipid membranes using solid-state NMR methods that are now being extended to membrane proteins.

nmr1Current focus is on the structure & interactions of amyloid peptides from Alzheimer’s disease, pore-forming toxins and antibiotic peptides in model biological membranes. Together with other multidisciplinary research groups we investigate biological macromolecules, geopolymers and ionic liquids for pharmaceutical & industrial applications.

Selected Publications:

  1. Separovic F.; Smith R.; Yannoni C.S.; Cornell B.A., J. Amer. Chem. Soc. 1990, 112, 8324-8
  2. Separovic F.; Gehrmann J.; Milne T.; Cornell B.A.; Lin S.; Smith R., Biophys. J. 1994, 67, 1495-500
  3. Separovic F.; Gawrisch K., Biophys. J. 1996, 71, 274-82
  4. Separovic, F.; Ashida, J.; Woolf, T.; Smith, R.; Terao, T., Chem. Phys. Lett. 1999, 303, 493-8
  5. Lam, Y.-H.; Wassall, S.R.; Morton, C.J.; Smith, R.; Separovic, F., Biophys. J. 2001, 81, 2752-61
  6. Bonev, B.B.; Lam, Y-H.; Anderluh, G.; Watts, A.; Norton, R.S.; Separovic F., Biophys. J. 2003, 84, 2382-92
  7. Lau, T.L.; Ambroggio, E.E.; Tew, D.J.; Cappai, R.; Masters, C.L.; Fidelio, G.D.; Barnham, K.J.; Separovic, F., J. Mol. Biol., 2006, 356, 759-70
  8. Fraser, S.J.; Rose, R.; Hattarki, M.K.; Hartley, P.G.; Dolezal, O.; Dawson, R.M.; Separovic, F.; Polyzos, A., Soft Matter, 2011, 7, 6125-34
  9. Sani, M.-A.; Henriques, S.T.; Weber, D.K.; Separovic, F., J. Biol. Chem., 2015, 290, 19853-62
  10. Karas, J.A.; Patil, N.A.; Tailhades, J.; Sani, M.-A.; Scanlon, D.B.; Forbes, B.E.; Gardiner, J.; Separovic, F.; Wade J.D.; Hossain, M.A., Angew. Chem. Int. Ed. 2016, 55, 14743-7

Book: Advances in Biological Solid-State NMR: Proteins and Membrane-Active Peptides (2014) Separovic, F. and Naito, A.