Separovic Research Group

NMR and Structural Studies of Membrane Peptides

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NMR and Structural Studies of Membrane Proteins


Advancements in bio/nano-technology require an inter-disciplinary approach and insight is needed from studies of biology at the molecular level. In collaboration with other multidisciplinary research groups we are providing insight into the biophysical chemistry of membrane-active peptides and proteins relevant to disease states and treatments.


Our laboratory is studying the structure-function relationships of macromolecular assemblies and biological systems at the molecular 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 structure and dynamics of membrane polypeptides to determine their mechanism of activity.


The structures of many biological systems cannot be obtained by traditional methods. Many systems are simply too large for solution-state NMR or have not been crystallized for X-ray diffraction. Solid-state NMR experiments have been designed for the structural determination of molecular systems that do not lend themselves to solution-state NMR and crystallographic methods. These methods can be applied to study the structure and dynamics of crystalline powders and biological membranes. For example, structures of powder samples can be determined and compared to single crystal X-ray structures of the same compound. Similarly, structural information for colloidal and membrane dispersions which undergo anisotropic motion and protein complexes which precipitate out of solution has been obtained using novel solid-state NMR methods.


Our primary research interest is the determination of the structure and dynamics of membrane components in situ, using solid-state NMR as the main technique. We have determined the molecular structure of the antibiotic gramicidin A and the bee toxin melittin within phospholipid membranes using solid-state NMR spectroscopy. Both gramicidin A and melittin form membrane ion channels and the techniques used to study these polypeptides are being extended to other integral membrane proteins. Together with researchers from CSIRO, industry and other international laboratories, we are studying biological macromolecules, geopolymers and ionic liquids with a range of pharmaceutical and industrial applications. Currently our main focus is the structure and interactions of amyloid peptides from Alzheimer’s disease, pore-forming toxins and antibiotic peptides in model biological membranes.


For further information on research projects, see:

http://www.chemistry.unimelb.edu.au/staff/fs/research/currentprojects.php


Selected Publications :


   1. Separovic F.; Smith R.; Yannoni C.S.; Cornell B.A., J. Amer. Chem. Soc. 1990, 112, 8324-8

   2. Smith R.; Separovic F.; Milne T.J.; Whittaker A.; Bennett F.M.; Cornell B.A.; Makriyannis A., J. Mol. Biol. 1994, 241, 456-66

   3. Separovic F.; Gehrmann J.; Milne T.; Cornell B.A.; Lin S.; Smith R., Biophys. J. 1994, 67, 1495-500

   4. Separovic F.; Gawrisch K., Biophys. J. 1996, 71, 274-82

   5. Separovic, F.; Ashida, J.; Woolf, T.; Smith, R.; Terao, T., Chem. Phys. Lett. 1999, 303, 493-8

   6. Lam, Y.-H.; Wassall, S.R.; Morton, C.J.; Smith, R.; Separovic, F., Biophys. J. 2001, 81, 2752-2761

   7. Bonev, B.B.; Lam, Y-H.; Anderluch, G.; Watts, A.; Norton, R.S.; Separovic F., Biophys. J. 2003, 84 2382-92

   8. 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, 759-770

   9. Drechsler, A.; Potrich, C.; Sabo, J.K.; Frisanco, M.; Guella, G.; Serra, M.D.; Anderluh, G.; Separovic, F.; Norton, R.S., Biochemistry, 2006, 45, 1818-1828

  10. 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, 8557-8565

 

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