How cytidylyltransferase uses an amphipathic helix to sense membrane phospholipid composition.
CT responds to properties of PC-depleted membranes: increased negative charge density, which concentrates the enzyme at the membrane surface, and lipid packing perturbations, which create holes in the membrane surface into which the hydrophobic side chains of the amphipathic helix of domain M can intercalate. The PC-deficient lipid surface appears capable of catalysing the folding of domain M into an alpha-helix. The determinants on domain M which create a preference for anionic lipids are: (i) strips of interfacial lysines; (ii) three serines within the non-polar face; (iii) three interfacial glutamates whose protonation state appears to be sensitive to the surface charge. Phosphorylation of the domain adjacent to domain M decreases the membrane affinity of the amphipathic helix, perhaps by an ion-pairing competition. The mechanism whereby the stabilization of an alpha-helical conformation of domain M is transduced into a conformational change in the catalytic domain is the key question for future exploration.
Cornell
R B
RB
Institute of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, B.C., Canada.
D000595:Amino Acid Sequence; D019916:Choline-Phosphate Cytidylyltransferase / Q000737:chemistry* / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D008051:Lipid Bilayers; D008563:Membrane Lipids; D010743:Phospholipids; D019916:Choline-Phosphate Cytidylyltransferase