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Department of Molecular Biology and Biochemistry
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Rosemary B. Cornell

Professor Emeritus
Molecular Biology & Biochemistry
Science

Areas of interest

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.

Education

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

Selected Publications

  • Ramezanpour, M., Lee, J., Taneva, S., Tieleman, D.P., Cornell, R.B. (2018) An auto-inhibitory helix in CTP:phosphocholine cytidylyltransferase hijacks the catalytic residue and constrains a pliable, domain-bridging helix pair.  J. Biol. Chem. 293: 7070-7084. 
  • Cornell, R.B. and Antonny, B. (2018) CCTalpha Commands Phospholipid Homeostasis from the Nucleus.  Devel. Cell 45:419-420
  • Cornell, R. B. (2016) Membrane lipid compositional sensing by the inducible amphipathic helix of CCT. Biochim. Biophys. Acta
  • Cornell, R.B. and Ridgway, N.D.  (2015) CTP: phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis. Prog. Lipid Res. 59: 147-171.
  • Cornell, R. B., Ridgway, N.D. (2015) CTPhosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis. Prog. Lipid. Res. 59: 147-171.
  • Lee, J., Taneva, S.G., Holland, B., Tieleman, D.P., and Cornell, R.B. (2014) Structural basis for auto-inhibition of CTP: phosphocholine cytidylyltransferase (CCT), the regulatory enzyme in phosphatidylcholine synthesis. J. Biol. Chem. 289: 1742-1755.
  • Chong, S. H., Taneva, S.G., Lee, J.M.C., and Cornell, R.B. (2014) The curvature sensitivity of membrane-binding amphipathic helices can be modulated by the charge on a flanking region. Biochemistry 53: 450-461.
  • Huang, H.K-H., Taneva, S.G., Lee, J., Silva, L.P., Schriemer, D.C., and Cornell, R.B. (2013) The membrane-binding domain of an amphitropic enzyme suppresses catalysis by interaction with an amphipathic helix flanking its active site. J. Mol. Biol. 425: 1546-1564.
  • Ding, Z., Taneva, S.G., Huang, H. K-H, Campbell, S.A., Semenec, L., Chen, N., Cornell, R.B. (2012) A 22mer segment in the structurally pliable regulatory domain of metazoan CTP: phosphocholine cytidylyltransferase facilitates both silencing and activating functions. J. Biol. Chem. 286: 38980-38991.
  • Taneva, S.G. Lee, J.M.C. Cornell, R.B. (2012) The amphipathic helix of an enzyme that regulates phosphatidylcholine synthesis remodels membranes into highly curved nanotubules. Biochim. Biophys. Acta -Biomembranes, 1818:1173-1186.
  • Dennis, M.K., Taneva, S.G., Cornell, R.B. (2011) The intrinsically disordered nuclear localization signal and phosphorylation segments distinguish the membrane affinity of two cytidylyltransferase isoforms. J. Biol. Chem. 286: 12349-12360.
  • Zahedi, B., Beaulieu, N., Goo, H-J., Kay R. J., Cornell, R.B. (2011) Phosphoinositide detection by RasGRP1 directly couples the PI 3-kinase and Ras signaling pathways at the plasma membrane. J. Biol. Chem. 286:12712-12723.
  • Jaeyong Lee, J.E. Johnson, Z. Ding, M. Paetzel, R. B. Cornell (2009) Crystal Structure of CTP:phosphocholine cytidylyltransferase catalytic domain novel catalytic residues within a highly conserved transferase active site fold. J. Biol. Chem. 284: 33535-33548.
  • Taneva, S.G., Dennis, M.K., Ding, Z., Smith, J.L., Cornell, R.B. (2008) Contribution of each membrane binding domain of the CTP: Phosphocholine Cytidylyltransferase-a dimer to its activation, membrane binding, and membrane cross-bridging. J. Biol. Chem. 283: 28137-28148.
  • Gehrig, K., Cornell, R.B., Ridgway, N. (2008) Expansion of the nucleoplasmic reticulum requires the coordinated activity of lamins and CTP:phosphocholine cytidylyltransferase-a.Molec. Biol. Cell. 19: 237-47.
  • Cornell, R.B. and Taneva, S. (2006) Amphipathic helices as mediators of the membrane interaction of amphitropic proteins, and as modulators of bilayer physical properties. Current Peptide and Protein Research7: 539-552.
  • Kitos,T.E., Choy, C.M.Y., and Cornell, R.B. (2006) Angiotensin stimulates phosphatidylcholine
  • synthesis via a pathway involving diacylglycerol, protein kinase C, ERK1/2, and CTP: phosphocholine cytidylyltransferase. Biochim. Biophys. Acta.,1761: 272-279.
  • Bogan, M.J., Agnes, G.R., Pio, F., Cornell, R.B. (2005) Interdomain and membrane interactions of CTP: Phosphocholine Cytidylyltransferase revealed via limited proteolysis and mass spectrometry.  J. Biol. Chem.280: 19613 - 19624.
  • Taneva, S., Johnson, J.E., and Cornell, R.B.* (2003) Lipid-Induced Conformational Switch in the Membrane Binding Domain of CTP:Phosphocholine Cytidylyltransferase: A Circular Dichroism Study. Biochemistry42, 11768-11776.
  • Johnson, J.E., Xie, M., Singh, L., Edge, R., & Cornell, R.B.* (2003) Both acidic and basic amino acids in an amphitropic enzyme dictate its selectivity for anionic membranes. J. Biol. Chem.278: 514-522.
  • Cornell, R.B.* & Northwood, I.C. (2000) Regulation of CTP:phosphocholine cytidylyltransferase by amphitropism and relocalization. Trends Biochem. Sci. 25: 441-447.
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