Research Guides

Study of membrane protein complexes 

Membrane protein complexes are notoriously difficult to study, particularly those that contain both membrane and soluble protein subunits.  This is because, in order to maintain solubility, large quantities of detergent are required. 

In 2008 we showed that  membrane protein complexes could be liberated from detergent micelles introduced into the mass spectrometer in electrospray droplets. These experiments paved the way for the study of many different membrane protein assemblies including lipid flippases, ion channels and G-protein coupled receptors. 

Understanding relationships between these proteins and their lipid surroundings now forms the basis of our current research programmes which are informing lipid mediated protein interactions, antibiotic resistance mechanisms and drug discovery more broadly.

J. R. Bolla, J. B. Sauer, D. Wu, S. Mehmood, T. M. Allison and C. V. Robinson.
Direct observation of the influence of cardiolipin and antibiotics on lipid II binding to MurJ
Nat Chem, 2018, 10, 363–371  doi:10.1038/nchem.2919

K. Gupta, J. Li, I. Liko, J. Gault, C. Bechara, D. Wu, J. T. S. Hopper, K. Giles, J. L. P. Benesch and C. V. Robinson.
Identifying key membrane protein lipid interactions using mass spectrometry.
Nat Protoc, 2018, (5): 1106-1120 doi: 10.1038/nprot.2018.014 

K. Gupta, J. A. Donlan, J. T. Hopper, P. Uzdavinys, M. Landreh, W. B.Struwe, D. Drew, A. J. Baldwin, P.J. Stansfeld, C.V. Robinson.
The role of interfacial lipids in stabilizing membrane protein oligomers.
Nature, 2017, 541: 421-424

S. Ambrose , N. G. Housden, K. Gupta, J. Fan, P. White, H-Y Yen, J. Marcoux, C. Kleanthous,  J. T. S. Hopper and C. V. Robinson.
Native Desorption Electrospray Ionization Liberates Soluble and Membrane Protein Complexes from Surfaces.
Angew Chem Int Ed Engl., 2017, 56(46):14463-14468

I. Liko, M. T. Degiacomi, S. Mohammed, S. Yoshikawa, C. Schmidt and C. V. Robinson.
Dimer interface of bovine cytochrome c oxidase is influenced by local posttranslational modifications and lipid binding.
Proc Natl Acad Sci USA, 2016, 113(29): 8230-8235