Title

Membrane Fluidity Is A Key Modulator Of Membrane Binding, Insertion, And Activity Of 5-Lipoxygenase

Abstract

Mammalian 5-lipoxygenase (5-LO) catalyzes conversion of arachidonic acid 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 interactions 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 (PARC). A fraction of tryptophans of 5-LO penetrate into the hydrocarbon region of fluid PARC membranes, but not into solid 1 ,2-dipalmitoyl-sn-glycero-S-phosphocholine membranes. Our data lead to a novel concept of membrane binding and activation of 5-LO, suggesting that arachidonic-acid-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 data presented in this article and earlier data allow construction of a model for membrane-bound 5-LO, including the angular orientation and membrane insertion of the protein. © 2005 by the Biophysical Society.

Publication Date

1-1-2005

Publication Title

Biophysical Journal

Volume

88

Issue

6

Number of Pages

4084-4094

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1529/biophysj.104.056788

Socpus ID

22244452942 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/22244452942

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