Membrane lipid compositional sensing by the inducible amphipathic helix of CCT

Biochim Biophys Acta. 2016 Aug;1861(8 Pt B):847-861. doi: 10.1016/j.bbalip.2015.12.022. Epub 2015 Dec 31.


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.

Keywords: Amphipathic helix; Amphitropism; Cytidylyltransferase; Lipid sensing; Membrane surface.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biophysical Phenomena
  • Choline-Phosphate Cytidylyltransferase / chemistry*
  • Choline-Phosphate Cytidylyltransferase / physiology*
  • Humans
  • Mechanotransduction, Cellular / physiology*
  • Membrane Lipids / chemistry*
  • Membrane Lipids / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary / physiology
  • Protein Structure, Tertiary


  • Membrane Lipids
  • Choline-Phosphate Cytidylyltransferase