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Biophys. J. BioFAST: First Published March 18, 2005. doi:10.1529/biophysj.104.056788
© 2005 by the Biophysical Society.

A more recent version of this article appeared on June 1, 2005.
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MEMBRANES

Membrane Fluidity Is a Key Modulator of Membrane Binding, Insertion, and Activity of 5-Lipoxygenase

Abhay H. Pande 1, Shan Qin 1 and Suren A. Tatulian 1*

1 University of Central Florida

* To whom correspondence should be addressed. E-mail: statulia{at}mail.ucf.edu.

Submitted on November 22, 2004
Revised on February 14, 2005
Accepted on 16 March 2005


  Abstract
Mammalian 5-lipoxygenase (5-LO) catalyzes conversion of arachidonic acid (AA) to leukotrienes, potent mediators of inflammation and allergy. Upon cell stimulation, 5-LO selectively binds to nuclear membranes and becomes activated, yet the mechanism of recruitment of 5-LO to nuclear membranes and the mode of 5-LO-membrane interaction are poorly understood. Here we show that membrane fluidity is an important determinant of membrane binding strength of 5-LO, penetration into the membrane hydrophobic core, and activity of the enzyme. The membrane binding strength and activity of 5-LO increase with the degree of lipid acyl chain cis-unsaturation and reach a plateau with 1-palmitoyl-2-arachidonolyl-sn-glycero-3-phosphocholine (PAPC). A fraction of tryptophans of 5-LO penetrate into the hydrocarbon region of fluid PAPC membranes, but not into solid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine membranes. Our data lead to a novel concept of membrane binding and activation of 5-LO, suggesting that AA-containing lipids, which are present in nuclear membranes at higher fractions than in other cellular membranes, may facilitate preferential membrane binding and insertion of 5-LO through increased membrane fluidity and may thereby modulate the activity of the enzyme. The present and earlier data allow construction of a model for membrane-bound 5-LO, including the angular orientation and membrane insertion of the protein.

Key Words: 5-lipoxygenase, activity, insertion, membrane binding, membrane fluidity




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Copyright © 2005 by the Biophysical Society.