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Membrane Protein Folding and Interactions

Developing methods for describing the assembly, interactions and three-dimensional structures of membrane proteins is the main focus of work in the lab. We use a wide-range of biochemical, computational, and biophysical techniques, including solution-state NMR spectroscopy. Of particular interest are membrane proteins involved in immune response and cancer developement.

MHC_TM_assembly

Figure: Schematic summarizing the roles of TM domains in the assembly of the Class II Major Histocompatibility complex, as described in three of our papers below:

  1. Dixon, A.M., Drake, L., Hughes, K.T., Sargent, E., Hunt, D., Harton, J.A., Drake, J.R. Differential Transmembrane Domain GxxxG Motif Pairing Impacts MHC Class II Structure, J. Biol. Chem., 2014, 289, p. 11695-703
  2. King, G. and Dixon, A.M. Evidence for Role of Transmembrane Helix-Helix Interactions in the Assembly of the Class II Major Histocompatibility Complex, Molecular BioSystems, 2010, 6, p. 1650-1661
  3. Dixon, A. M., Stanley B.J., Matthews, E.E., Dawson, J.P., Engelman, D.M., Invariant chain transmembrane domain trimerization: A step in MHC class II assembly, Biochemistry, 2006, 45, p. 5228-5234.

More generally, we are also interested in how protein-protein and protein-lipid interactions occur in membrane bilayers, and what molecular properties control these interactions. The papers below summarize some of our recent work in these areas.

  1. Breeze, E., Dzimitrowicz, N., Kriechbaumer, V., Brooks, R., Botchway, S.W., Brady, J.P., Hawes, C., Dixon, A.M., Schnell, J.R., Fricker, M.D., Frigerio, L., A C-terminal amphipathic helix is necessary for the in vivo tubule-shaping function of a plant reticulon, Proc. Natl. Acad. Sci., 2016, 113, 10902-10907.
  2. Lock, A., Forfar, R., Weston, C., Bowsher, L., Upton, G.J.G., Reynolds, C.A., Ladds, G., Dixon, A.M., One Motif to Bind Them: A Small-XXX-Small Motif Affects Transmembrane Domain 1 Oligomerization, Function, Localization, and Cross-talk Between Two Yeast GPCRs, Biochimica et Biophysica Acta – Biomembranes, 2014, 1838, p. 3036-3051.
  3. Beevers, A.J., Nash, A., Salazar-Cancino, M., Scott, D.J., Notman, R., and Dixon, A.M., Effects of the Oncogenic V664E Mutation on Membrane Insertion, Structure, and Sequence-dependent Interactions of the Neu Transmembrane Domain in Micelles and Model Memebranes: An Integrated Biophysical and Simulation Study, Biochemistry, 2012, 51, p. 2558-2568.
  4. Jenei, Z.A., Warren, G.Z.L., Hasan, M., Zammit, V.A. and Dixon, A.M. Packing of Transmembrane Domain 2 of Carnitine Palmitoyltransferase-1A affects Oligomerization and Malonyl-CoA Sensitivity of the Mitochondrial Outer Membrane Protein, FASEB J, 2011, 25, p. 4522-4530.
  5. King, G., Oates, J., Patel, D., van den Berg, H., and Dixon, A.M., Towards a Structural Understanding of the Smallest Known Oncoprotein: Investigation of the Bovine Papillomavirus E5 Protein using Solution-state NMR, BBA - Biomembranes, 2011, 1808, p. 1493-1501.