2WEX

Crystal structure of human apoM in complex with glycerol 1- myristic acid

2WEX の概要

• エントリーDOI: 10.2210/pdb2wex/pdb
• 関連するPDBエントリー: 2WEW
• 分子名称: APOLIPOPROTEIN M, (2R)-2,3-dihydroxypropyl tetradecanoate, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: lipid transport, ligand-binding specificity, glycoprotein, myristic acid, hdl, lipocalin, transport, lipoproteins
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Secreted: O95445
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19607.31

構造登録者

Sevvana, M.,Ahnstrom, J.,Egerer-Sieber, C.,Dahlback, B.,Muller, Y.A. (登録日: 2009-04-02, 公開日: 2009-09-15, 最終更新日: 2024-11-20)

主引用文献

Sevvana, M.,Ahnstrom, J.,Egerer-Sieber, C.,Lange, H.A.,Dahlback, B.,Muller, Y.A.
Serendipitous Fatty Acid Binding Reveals the Structural Determinants for Ligand Recognition in Apolipoprotein M.
J.Mol.Biol., 393:920-, 2009

PubMed Abstract: 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.

PubMed: 19733574
DOI: 10.1016/J.JMB.2009.08.071

実験手法

X-RAY DIFFRACTION (2 Å)