B.Sc., Houghton College Ph.D., University of Pennsylvania

Membrane protein-lipids interaction

Membrane biochemistry and Structural Biology; Regulation of peripheral membrane proteins by lipid interactions

Regulatory enzymes that control metabolism are multi-domain structures whose catalytic sites are often suppressed by inter-domain interactions until some cellular signal binds and disrupts that inhibitory interaction. Many metabolic enzymes and signal-transducing proteins are regulated by membrane binding, which triggers an ON switch. One of these is CTP: phosphocholine cytidylyltransferase (CCT), which catalyzes a key regulatory step in phosphatidylcholine synthesis. Membrane binding and activation of CCT is promoted by increases in minor lipid species such as fatty acids and diacylglycerol, and by dephosphorylation of CCT. The conformational changes in the enzyme associated with its activation are being probed by X-ray diffraction, fluorescence spectroscopy, circular dichroism, mass spec, and molecular dynamics simulations.

Cornell, R. B. Membrane lipid compositional sensing by the inducible amphipathic helix of CCT. Biochim. Biophys. Acta, in press. 2016 Lee, J., Taneva, S.G., Holland, B., Tieleman, D.P., and Cornell, R.B. Structural basis for auto-inhibition of CTP: phosphocholine cytidylyltransferase (CCT), the regulatory enzyme in phosphatidylcholine synthesis. J. Biol. Chem. 2014 Huang HK, Taneva SG, Lee J, Silva LP, Schriemer DC, Cornell RB. The Membrane-Binding Domain of an Amphitropic Enzyme Suppresses Catalysis by Contact with an Amphipathic Helix Flanking Its Active Site. J Mol Biol. 2012