title: Membrane lipid compositional sensing by the inducible amphipathic helix of CCT.
abstract: The amphipathic helical (AH) membrane binding motif is recognized as a major device for lipid compositional sensing. We explore the function and mechanism of sensing by the lipid biosynthetic enzyme, CTP:phosphocholine cytidylyltransferase (CCT). As the regulatory enzyme in phosphatidylcholine (PC) synthesis, CCT contributes to membrane PC homeostasis. CCT directly binds and inserts into the surface of bilayers that are deficient in PC and therefore enriched in lipids that enhance surface charge and/or create lipid packing voids. These two membrane physical properties induce the folding of the CCT M domain into a ≥60 residue AH. Membrane binding activates catalysis by a mechanism that has been partially deciphered. We review the evidence for CCT compositional sensing, and the membrane and protein determinants for lipid selective membrane-interactions. We consider the factors that promote the binding of CCT isoforms to the membranes of the ER, nuclear envelope, or lipid droplets, but exclude CCT from other organelles and the plasma membrane. The CCT sensing mechanism is compared with several other proteins that use an AH motif for membrane compositional sensing. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, B.C. V5A 1S6, Canada. Electronic address: cornell@sfu.ca.
authors.forename: Rosemary B
authors.initials: RB
authors.lastname: Cornell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055592:Biophysical Phenomena; D019916:Choline-Phosphate Cytidylyltransferase / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary
chemical_list: D008563:Membrane Lipids; D019916:Choline-Phosphate Cytidylyltransferase
keywords: Amphipathic helix; Amphitropism; Cytidylyltransferase; Lipid sensing; Membrane surface