Crystal structure of a calcium-phospholipid binding domain from cytosolic phospholipase A2

被引:236
作者
Perisic, O
Fong, S
Lynch, DE
Bycroft, M
Williams, RL
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
[2] MRC Ctr, Ctr Prot Engn, Cambridge CB2 2QH, England
基金
英国医学研究理事会;
关键词
D O I
10.1074/jbc.273.3.1596
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cytosolic phospholipase A2 (cPLA2) is a calcium-sensitive 85-kDa enzyme that hydrolyzes arachidonic acid-containing membrane phospholipids to initiate the bio synthesis 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-Angstrom x-ray crystal structure of this C2 domain was solved by multiple isomorphous replacement and reveals a beta-sandwich with the same topology as the C2 domain from phosphoinositide-specific phospholipase C delta 1, 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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页码:1596 / 1604
页数:9
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