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. Separovic Lab @ Bio21 in collaboration with other multidisciplinary research groups provide insight into the biophysical chemistry of membrane-active peptides and proteins relevant to disease states and treatments.

We are studying the structure-function relationships of macromolecular assemblies and biological systems at the atomistic level through the use of powerful solid-state NMR (nuclear magnetic resonance) methods. NMR spectroscopy, complemented by a range of biophysical techniques, is being used to determine the mechanism of action of membrane polypeptides.

Solid-state NMR is used to study the structure & dynamics of crystalline powders, protein complexes and biological membranes. 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.

nmr1 Together with researchers from CSIRO, industry and international laboratories, we are studying biological macromolecules, geopolymers and ionic liquids for pharmaceutical and industrial applications. Currently our main focus is on the structure and interactions of amyloid peptides from Alzheimer’s disease, pore-forming toxins and antibiotic peptides in model biological membranes.

Selected Publications:

Recent book, Advances in Biological Solid-State NMR: Proteins and Membrane-Active Peptides

  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. Gehman, J.D.; Luc, F.; Hall, K., Lee, T.-H.; Boland, M.P.; Pukala, T.L.; Bowie, J.H.; Aguilar, M.I.; Separovic, F., Biochemistry, 47, 2008, 8557-65
  9. Fraser, S.J.; Rose, R.; Hattarki, M.K.; Hartley, P.G.; Dolezal, O.; Dawson, R.M.; Separovic, F.; Polyzos, A., Soft Matter, 7, 2011, 6125-34
  10. Sani, M.-A.; Henriques, S.T.; Weber, D.K.; Separovic, F., J. Biol. Chem., 290, 2015, 19853-62