Phosphatidic Acid: An Electrostatic/Hydrogen-Bond Switch?
Phosphatidic acid (PA) has been shown to be an important bioactive lipid that is specifically recognized by various proteins. As such, it plays a crucial role in cellular signaling in all eukaryotes. An important determinant for PA’s role in its diverse functions is its anionic headgroup that resides very close to the hydrophobic interior of the lipid bilayer. In this chapter, we describe a new model, the electrostatic/hydrogen-bond switch that describes PA’s ionization properties and its specific interaction with proteins. Furthermore, we will allude to the broader implications of the model for all phosphomonoester moieties found in biological compounds. Recent data in support of the model, as well as biological predictions arising from it, are also discussed.
KeywordsPhosphatidic Acid Phosphatidic Acid Magic Angle Spin Anionic Lipid Basic Amino Acid Residue
The authors thank Ben de Kruijff, Koert N.J. Burger, and Teun Munnik for their interest and enthusiasm in the research that led up to this chapter. Christian Kandt is acknowledged for his superb artwork. EEK is indebted to Satyendra Kumar for creating the academic atmosphere in which the writing of this chapter was made possible.
EEK acknowledges financial support from the US National Science Foundation grants DMR-0637221 and CHE-0724082 as well as a Research Challenge award from the Ohio Board of Regents. CT acknowledges NWO for financial support through CW-Vidi grant 700.56.429.
The authors apologize to those authors whose original work is not cited here due to length considerations.
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