Document Detail

Serendipitous fatty acid binding reveals the structural determinants for ligand recognition in apolipoprotein M.
MedLine Citation:
PMID:  19733574     Owner:  NLM     Status:  MEDLINE    
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.
Madhumati Sevvana; Josefin Ahnström; Claudia Egerer-Sieber; Harald A Lange; Björn Dahlbäck; Yves A Muller
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-04
Journal Detail:
Title:  Journal of molecular biology     Volume:  393     ISSN:  1089-8638     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-19     Completed Date:  2009-11-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  920-36     Citation Subset:  IM    
Lehrstuhl für Biotechnik, Department of Biology, Friedrich-Alexander-University Erlangen-Nuremberg, Im IZMP, Henkestr. 91, D-91052 Erlangen, Germany.
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MeSH Terms
Amino Acid Sequence
Apolipoproteins / chemistry*,  metabolism
Crystallography, X-Ray
Fatty Acids* / chemistry,  metabolism
Gas Chromatography-Mass Spectrometry
Inhibitory Concentration 50
Lipid Bilayers / chemistry
Lipocalins / chemistry,  metabolism
Molecular Sequence Data
Protein Binding
Protein Conformation*
Protein Folding
Sequence Alignment
Spectrometry, Fluorescence
Reg. No./Substance:
0/APOM protein, human; 0/Apolipoproteins; 0/Fatty Acids; 0/Ligands; 0/Lipid Bilayers; 0/Lipocalins

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