Source:http://linkedlifedata.com/resource/pubmed/id/11796736
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
15
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pubmed:dateCreated |
2002-4-8
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pubmed:abstractText |
The activation of 5-lipoxygenase (5-LO) involves its calcium-dependent translocation to the nuclear envelope, where it catalyzes the two-step transformation of arachidonic acid into leukotriene A(4), leading to the synthesis of various leukotrienes. To understand the mechanism by which 5-LO is specifically targeted to the nuclear envelope, we studied the membrane binding properties of the amino-terminal domain of 5-LO, which has been proposed to have a C2 domain-like structure. The model building, electrostatic potential calculation, and in vitro membrane binding studies of the isolated C2-like domain of 5-LO and selected mutants show that this Ca(2+)-dependent domain selectively binds zwitterionic phosphatidylcholine, which is conferred by tryptophan residues (Trp(13), Trp(75), and Trp(102)) located in the putative Ca(2+)-binding loops. The spatiotemporal dynamics of the enhanced green fluorescence protein-tagged C2-like domain of 5-LO and mutants in living cells also show that the phosphatidylcholine selectivity of the C2-like domain accounts for the specific targeting of 5-LO to the nuclear envelope. Together, these results show that the C2-like domain of 5-LO is a genuine Ca(2+)-dependent membrane-targeting domain and that the subcellular localization of the domain is governed in large part by its membrane binding properties.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13167-74
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11796736-Amino Acid Sequence,
pubmed-meshheading:11796736-Arachidonate 5-Lipoxygenase,
pubmed-meshheading:11796736-Calcium,
pubmed-meshheading:11796736-Cell Line,
pubmed-meshheading:11796736-Humans,
pubmed-meshheading:11796736-Models, Molecular,
pubmed-meshheading:11796736-Molecular Sequence Data,
pubmed-meshheading:11796736-Mutagenesis, Site-Directed,
pubmed-meshheading:11796736-Protein Binding,
pubmed-meshheading:11796736-Protein Conformation,
pubmed-meshheading:11796736-Sequence Homology, Amino Acid,
pubmed-meshheading:11796736-Static Electricity,
pubmed-meshheading:11796736-Subcellular Fractions,
pubmed-meshheading:11796736-Surface Plasmon Resonance
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pubmed:year |
2002
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pubmed:articleTitle |
Molecular basis of the specific subcellular localization of the C2-like domain of 5-lipoxygenase.
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pubmed:affiliation |
Department of Chemistry, University of Illinois, 845 West Taylor Street, Chicago, IL 60607-7061, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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