Journal of Biological Chemistry
Volume 282, Issue 15, 13 April 2007, Pages 11356-11364
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Membrane Transport, Structure, Function, and Biogenesis
An Electrostatic/Hydrogen Bond Switch as the Basis for the Specific Interaction of Phosphatidic Acid with Proteins*

https://doi.org/10.1074/jbc.M609737200Get rights and content
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Phosphatidic acid (PA) is a minor but important phospholipid that, through specific interactions with proteins, plays a central role in several key cellular processes. The simple yet unique structure of PA, carrying just a phosphomonoester head group, suggests an important role for interactions with the positively charged essential residues in these proteins. We analyzed by solid-state magic angle spinning 31P NMR and molecular dynamics simulations the interaction of low concentrations of PA in model membranes with positively charged side chains of membrane-interacting peptides. Surprisingly, lysine and arginine residues increase the charge of PA, predominantly by forming hydrogen bonds with the phosphate of PA, thereby stabilizing the protein-lipid interaction. Our results demonstrate that this electrostatic/hydrogen bond switch turns the phosphate of PA into an effective and preferred docking site for lysine and arginine residues. In combination with the special packing properties of PA, PA may well be nature's preferred membrane lipid for interfacial insertion of positively charged membrane protein domains.

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*

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental material.

2

Supported by Netherlands Organization for Scientific Research/FOM/ALW, “Fysische Biologie” program.

3

An Alberta Heritage Foundation for Medical Research Senior Scholar and Canadian Institutes of Health Research (CIHR) New Investigator. Work in this group was supported by Natural Science and Engineering Research Council and CIHR.

4

Supported by Netherlands Organization for Scientific Research, Veni Grant CW 700.52.401 and Vidi Grant CW 700.56.429.

5

Work in this laboratory was supported by the Netherlands Organization for Scientific Research Grants 813.06.003, 863.04.004, 864.05.001, and 810-36.005 and the Royal Netherlands Academy of Arts and Sciences (KNAW).

6

Supported by the Human Frontier Science Program Organization and European Community Network Grant HPRN-CT-2002-00259.