Rosemary B. Cornell, Professor
B.Sc., Houghton College
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 proteins involved in signal transduction are amphitropic; i.e. they are regulated by reversible association with cell membranes. Membrane binding triggers an ON switch. One of these is CTP: phosphocholine cytidylyltransferase (CCT), which catalyzes a key regulatory step in phosphatidylcholine synthesis. We are investigating the interplay between CCT and membranes enriched in lipid mediators such as fatty acids and diacylglycerol. Membrane binding and activation of CCT is promoted by increases in membrane content of these minor lipid species, and by dephosphorylation of CCT's C-terminal tail. The conformational changes in the enzyme associated with its activation are being probed by X-ray diffraction, by spectroscopic tools such as fluorescence anisotropy and circular dichroism, and molecular dynamics simulations.