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Crystal Structure of a Calcium-Phospholipid Binding Domain from Cytosolic Phospholipase A2

Cytosolic phospholipase A2 (cPLA2) is a calcium-sensitive 85-kDa enzyme that hydrolyzes arachidonic acid-containing membrane phospholipids to initiate the biosynthesis of eicosanoids and platelet-activating factor, potent inflammatory mediators. The calcium-dependent activation of the enzyme is medi...

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Published in:The Journal of biological chemistry 1998-01, Vol.273 (3), p.1596-1604
Main Authors: Perisic, Olga, Fong, Sun, Lynch, Denise E., Bycroft, Mark, Williams, Roger L.
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Language:English
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cited_by cdi_FETCH-LOGICAL-c472t-da149cc0ebab8b1936714a6f3d0b361a5db287172fee6588857388479502d7da3
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container_title The Journal of biological chemistry
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creator Perisic, Olga
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description Cytosolic phospholipase A2 (cPLA2) is a calcium-sensitive 85-kDa enzyme that hydrolyzes arachidonic acid-containing membrane phospholipids to initiate the biosynthesis of eicosanoids and platelet-activating factor, potent inflammatory mediators. The calcium-dependent activation of the enzyme is mediated by an N-terminal C2 domain, which is responsible for calcium-dependent translocation of the enzyme to membranes and that enables the intact enzyme to hydrolyze membrane-resident substrates. The 2.4-Å x-ray crystal structure of this C2 domain was solved by multiple isomorphous replacement and reveals a β-sandwich with the same topology as the C2 domain from phosphoinositide-specific phospholipase Cδ1. Two clusters of exposed hydrophobic residues surround two adjacent calcium binding sites. This region, along with an adjoining strip of basic residues, appear to constitute the membrane binding motif. The structure provides a striking insight into the relative importance of hydrophobic and electrostatic components of membrane binding for cPLA2. Although hydrophobic interactions predominate for cPLA2, for other C2 domains such as in “conventional” protein kinase C and synaptotagmins, electrostatic forces prevail.
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subjects Amino Acid Sequence
Binding Sites
Calcium - metabolism
Cloning, Molecular
Crystallography, X-Ray
Cytosol - enzymology
Humans
Isoenzymes - metabolism
Models, Chemical
Models, Molecular
Molecular Sequence Data
Phospholipase C delta
Phospholipases A - chemistry
Phospholipases A2
Phospholipids - metabolism
Protein Structure, Secondary
Type C Phospholipases - metabolism
title Crystal Structure of a Calcium-Phospholipid Binding Domain from Cytosolic Phospholipase A2
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