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Diacylglycerol specifically blocks spontaneous integration of membrane proteins and allows detection of a

Yosuke Kawashima1, Emi Miyazaki, Matthias Müller

  • 1Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan.

The Journal of Biological Chemistry
|July 11, 2008
PubMed

Insights

Diacylglycerol (DAG) blocks spontaneous membrane protein integration, including Pf3 coat protein. This blockage is specific to DAG and its structure, not membrane curvature, and occurs in native vesicles.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Membrane Biology

Background:

  • Spontaneous integration of M13 procoat into liposomes is known to be inhibited by diacylglycerol (DAG).
  • Pf3 coat protein is another membrane protein believed to integrate spontaneously into liposomes.

Purpose of the Study:

  • To investigate the effect of diacylglycerol (DAG) on the spontaneous integration of Pf3 coat protein.
  • To elucidate the mechanism by which DAG inhibits spontaneous membrane protein integration.

Main Methods:

  • Testing the effect of DAG on Pf3 coat protein integration into liposomes.
  • Examining various lipid compounds similar to DAG and its derivatives.
  • Investigating the role of lipid A-derived integration factors.
  • Assessing DAG's effect in native membrane vesicles.

Main Results:

  • DAG inhibits the spontaneous integration of Pf3 coat protein at physiological concentrations.
  • DAG also blocks the integration of a membrane potential-independent mutant of Pf3 coat protein (3L-Pf3 coat).
  • The inhibitory effect is specific to DAG, with other lipids like fatty acids and monoacylglycerols showing no effect.
  • Shortening acyl chains in DAG retained inhibitory activity, but diheptanoylglycerol did not.
  • Triacylglycerol was more effective than DAG, but interfered with M13 procoat integration.
  • DAG inclusion made 3L-Pf3 coat integration dependent on a lipid A-derived factor.
  • DAG's bulky structure, not membrane curvature, is key to inhibition.
  • DAG's inhibitory effect was observed in native membrane vesicles.

Conclusions:

  • Diacylglycerol (DAG) specifically inhibits the spontaneous integration of membrane proteins like Pf3 coat.
  • The mechanism of inhibition involves DAG's bulky structure, not membrane curvature changes.
  • DAG's inhibitory action is relevant in both artificial liposomes and native membrane systems.

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