| Serendipitous fatty acid binding reveals the structural determinants for ligand recognition in apolipoprotein M. | |
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MedLine Citation:
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PMID: 19733574 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Apolipoprotein M (ApoM) is a 25-kDa HDL-associated apolipoprotein and a member of the lipocalin family of proteins. Mature apoM retains its signal peptide, which serves as a lipid anchor attaching apoM to the lipoproteins, thereby keeping it in the circulation. Studies in mice have suggested apoM to be antiatherogenic, but its physiological function is yet unknown. We have now determined the 1.95 A resolution crystal structure of recombinant human apoM expressed in Escherichia coli and made the unexpected discovery that apoM, although refolded from inclusion bodies, was in complex with fatty acids containing 14, 16 or 18 carbon atoms. ApoM displays the typical lipocalin fold characterised by an eight-stranded antiparallel beta-barrel that encloses an internal ligand-binding pocket. The crystal structures of two different complexes provide a detailed picture of the ligand-binding determinants of apoM. Additional fatty acid- and lipid-binding studies with apoM and the mutants apoM(W47F) and apoM(W100F) showed that sphingosine-1-phosphate is able to displace the bound fatty acids and efficiently quenched the intrinsic fluorescence with an IC(50) of 0.90 muM. Whereas the fatty acids bound in the crystal structure could be a mere consequence of recombinant protein production, the observed binding of sphingosine-1-phosphate might provide a key to a better understanding of the physiological function of apoM. |
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Authors:
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Madhumati Sevvana; Josefin Ahnström; Claudia Egerer-Sieber; Harald A Lange; Björn Dahlbäck; Yves A Muller |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-04 |
Journal Detail:
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Title: Journal of molecular biology Volume: 393 ISSN: 1089-8638 ISO Abbreviation: J. Mol. Biol. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-19 Completed Date: 2009-11-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985088R Medline TA: J Mol Biol Country: England |
Other Details:
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Languages: eng Pagination: 920-36 Citation Subset: IM |
Affiliation:
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Lehrstuhl für Biotechnik, Department of Biology, Friedrich-Alexander-University Erlangen-Nuremberg, Im IZMP, Henkestr. 91, D-91052 Erlangen, Germany. |
| Data Bank Information | |
Bank Name/Acc. No.:
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PDB/2WEW; 2WEX |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Apolipoproteins / chemistry*, metabolism Crystallography, X-Ray Fatty Acids* / chemistry, metabolism Gas Chromatography-Mass Spectrometry Humans Inhibitory Concentration 50 Ligands* Lipid Bilayers / chemistry Lipocalins / chemistry, metabolism Mice Molecular Sequence Data Protein Binding Protein Conformation* Protein Folding Sequence Alignment Spectrometry, Fluorescence |
| Chemical | |
Reg. No./Substance:
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0/APOM protein, human; 0/Apolipoproteins; 0/Fatty Acids; 0/Ligands; 0/Lipid Bilayers; 0/Lipocalins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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