Biophys J, February 2001, p. 789-800, Vol. 80, No. 2

Toward Understanding Interfacial Activation of Secretory Phospholipase A₂ (PLA₂): Membrane Surface Properties and Membrane-Induced Structural Changes in the Enzyme Contribute Synergistically to PLA₂ Activation

Section of Biochemistry and Biophysics, Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045 USA

Phospholipase A₂ (PLA₂) hydrolyzes phospholipids to free fatty acids and lysolipids and thus initiates the biosynthesis of eicosanoids and platelet-activating factor, potent mediators of inflammation, allergy, apoptosis, and tumorigenesis. The relative contributions of the physical properties of membranes and the structural changes in PLA₂ to the interfacial activation of PLA₂, that is, a strong increase in the lipolytic activity upon binding to the surface of phospholipid membranes or micelles, are not well understood. The present results demonstrate that both binding of PLA₂ to phospholipid bilayers and its activity are facilitated by membrane surface electrostatics. Higher PLA₂ activity toward negatively charged membranes is shown to result from stronger membrane-enzyme electrostatic interactions rather than selective hydrolysis of the acidic lipid. Phospholipid hydrolysis by PLA₂ is followed by preferential removal of the liberated lysolipid and accumulation of the fatty acid in the membrane that may predominantly modulate PLA₂ activity by affecting membrane electrostatics and/or morphology. The previously described induction of a flexible helical structure in PLA₂ during interfacial activation was more pronounced at higher negative charge densities of membranes. These findings identify a reciprocal relationship between the membrane surface properties, strength of membrane binding of PLA₂, membrane-induced structural changes in PLA₂, and the enzyme activation.

Biophys J, February 2001, p. 789-800, Vol. 80, No. 2
© 2001 by the Biophysical Society   0006-3495/01/02/789/12  $2.00

This article has been cited by other articles:

				J. Saegusa, N. Akakura, C.-Y. Wu, C. Hoogland, Z. Ma, K. S. Lam, F.-T. Liu, Y. K. Takada, and Y. Takada Pro-inflammatory Secretory Phospholipase A2 Type IIA Binds to Integrins {alpha}v{beta}3 and {alpha}4{beta}1 and Induces Proliferation of Monocytic Cells in an Integrin-dependent Manner J. Biol. Chem., September 19, 2008; 283(38): 26107 - 26115. [Abstract] [Full Text] [PDF]

				C. L. Wee, K. Balali-Mood, D. Gavaghan, and M. S. P. Sansom The Interaction of Phospholipase A2 with a Phospholipid Bilayer: Coarse-Grained Molecular Dynamics Simulations Biophys. J., August 15, 2008; 95(4): 1649 - 1657. [Abstract] [Full Text] [PDF]

				C. Code, Y. Domanov, A. Jutila, and P. K. J. Kinnunen Amyloid-Type Fiber Formation in Control of Enzyme Action: Interfacial Activation of Phospholipase A2 Biophys. J., July 1, 2008; 95(1): 215 - 224. [Abstract] [Full Text] [PDF]

				R. W. Bailey, E. D. Olson, M. P. Vu, T. J. Brueseke, L. Robertson, R. E. Christensen, K. H. Parker, A. M. Judd, and J. D. Bell Relationship between Membrane Physical Properties and Secretory Phospholipase A2 Hydrolysis Kinetics in S49 Cells during Ionophore-Induced Apoptosis Biophys. J., October 1, 2007; 93(7): 2350 - 2362. [Abstract] [Full Text] [PDF]

				S. Qin, A. H. Pande, K. N. Nemec, X. He, and S. A. Tatulian Evidence for the Regulatory Role of the N-terminal Helix of Secretory Phospholipase A2 from Studies on Native and Chimeric Proteins J. Biol. Chem., November 4, 2005; 280(44): 36773 - 36783. [Abstract] [Full Text] [PDF]

				W. Yan, C. M. Jenkins, X. Han, D. J. Mancuso, H. F. Sims, K. Yang, and R. W. Gross The Highly Selective Production of 2-Arachidonoyl Lysophosphatidylcholine Catalyzed by Purified Calcium-independent Phospholipase A2{gamma}: IDENTIFICATION OF A NOVEL ENZYMATIC MEDIATOR FOR THE GENERATION OF A KEY BRANCH POINT INTERMEDIATE IN EICOSANOID SIGNALING J. Biol. Chem., July 22, 2005; 280(29): 26669 - 26679. [Abstract] [Full Text] [PDF]

				L. B. Jensen, N. K. Burgess, D. D. Gonda, E. Spencer, H. A. Wilson-Ashworth, E. Driscoll, M. P. Vu, J. L. Fairbourn, A. M. Judd, and J. D. Bell Mechanisms Governing the Level of Susceptibility of Erythrocyte Membranes to Secretory Phospholipase A2 Biophys. J., April 1, 2005; 88(4): 2692 - 2705. [Abstract] [Full Text] [PDF]

				H. W.M Niessen, P. A.J Krijnen, C. A Visser, C. J.L.M Meijer, and C Erik Hack Type II secretory phospholipase A2 in cardiovascular disease: a mediator in atherosclerosis and ischemic damage to cardiomyocytes? Cardiovasc Res, October 15, 2003; 60(1): 68 - 77. [Abstract] [Full Text] [PDF]

				G. Zolese, M. Wozniak, P. Mariani, L. Saturni, E. Bertoli, and A. Ambrosini Different modulation of phospholipase A2 activity by saturated and monounsaturated N-acylethanolamines J. Lipid Res., April 1, 2003; 44(4): 742 - 753. [Abstract] [Full Text] [PDF]

				S. A. Tatulian Structural Effects of Covalent Inhibition of Phospholipase A2 Suggest Allosteric Coupling between Membrane Binding and Catalytic Sites Biophys. J., March 1, 2003; 84(3): 1773 - 1783. [Abstract] [Full Text] [PDF]

				L. K. Nielsen, K. Balashev, T. H. Callisen, and T. Bjornholm Influence of Product Phase Separation on Phospholipase A2 Hydrolysis of Supported Phospholipid Bilayers Studied by Force Microscopy Biophys. J., November 1, 2002; 83(5): 2617 - 2624. [Abstract] [Full Text] [PDF]