Thermodynamic and solution state NMR characterization of the binding of secondary and conjugated bile acids to STARD5

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• 作者：Danny L¨¦tourneau ; Aur¨¦lien Lorin ; Andr¨¦e Lefebvre ; J¨¦r?me Cabana ; Pierre Lavigne ; Jean-Guy LeHoux
• 关键词：CA ; cholic acid ; CDCA ; chenodeoxycholic acid ; DCA ; deoxycholic acid ; LCA ; lithocholic acid ; UDCA ; ursodeoxycholic acid ; TCA ; taurocholic acid ; GCA ; glycocholic acid ; TDCA ; taurodeoxycholic acid ; GDCA ; glycodeoxycholic acid ; NMR ; nuclear magnetic resonance
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2013
• 出版时间：November, 2013
• 年：2013
• 卷：1831
• 期：11
• 页码：1589-1599
• 全文大小：3015 K

文摘

STARD5 is a member of the STARD4 sub-family of START domain containing proteins specialized in the non-vesicular transport of lipids and sterols. We recently reported that STARD5 binds primary bile acids. Herein, we report on the biophysical and structural characterization of the binding of secondary and conjugated bile acids by STARD5 at physiological concentrations. We found that the absence of the 7¦Á-OH group and its epimerization increase the affinity of secondary bile acids for STARD5. According to NMR titration and molecular modeling, the affinity depends mainly on the number and positions of the steroid ring hydroxyl groups and to a lesser extent on the presence or type of bile acid side-chain conjugation. Primary and secondary bile acids have different binding modes and display different positioning within the STARD5 binding pocket. The relative STARD5 affinity for the different bile acids studied is: DCA > LCA > CDCA > GDCA > TDCA > CA > UDCA. TCA and GCA do not bind significantly to STARD5. The impact of the ligand chemical structure on the thermodynamics of binding is discussed. The discovery of these new ligands suggests that STARD5 is involved in the cellular response elicited by bile acids and offers many entry points to decipher its physiological role.