StAR-related lipid transfer domain protein 5 binds primary bile acids
| Autor: | Jean-Guy Lehoux, Vincent Frappier, Pierre Lavigne, Aurélien Lorin, Andrée Lefebvre, Rafael Najmanovich, Francis Gaudreault, Danny Létourneau |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Circular dichroism Magnetic Resonance Spectroscopy Stereochemistry Protein domain STARD4 QD415-436 Cholic Acid Chenodeoxycholic Acid Ligands Biochemistry Structure-Activity Relationship chemistry.chemical_compound Endocrinology Chenodeoxycholic acid Humans Cloning Molecular Binding site Research Articles bile acids lipid transport Binding Sites Protein Stability Isothermal titration calorimetry Cell Biology Reference Standards isothermal titration calorimetry circular dichroism Adaptor Proteins Vesicular Transport chemistry cholesterol metabolism Thermodynamics Farnesoid X receptor Carrier Proteins steroidogenic acute regulatory protein Heteronuclear single quantum coherence spectroscopy |
| Zdroj: | Journal of Lipid Research, Vol 53, Iss 12, Pp 2677-2689 (2012) |
| ISSN: | 0022-2275 |
| Popis: | Steroidogenic acute regulatory-related lipid transfer (START) domain proteins are involved in the nonvesicular intracellular transport of lipids and sterols. The STARD1 (STARD1 and STARD3) and STARD4 subfamilies (STARD4-6) have an internal cavity large enough to accommodate sterols. To provide a deeper understanding on the structural biology of this domain, the binding of sterols to STARD5, a member of the STARD4 subfamily, was monitored. The SAR by NMR [(1)H-(15)N heteronuclear single-quantum coherence (HSQC)] approach, complemented by circular dichroism (CD) and isothermal titration calorimetry (ITC), was used. Titration of STARD5 with cholic (CA) and chenodeoxycholic acid (CDCA), ligands of the farnesoid X receptor (FXR), leads to drastic perturbation of the (1)H-(15)N HSQC spectra and the identification of the residues in contact with those ligands. The most perturbed residues in presence of ligands are lining the internal cavity of the protein. Ka values of 1.8·10-(4) M(-1) and 6.3·10(4) M(-1) were measured for CA and CDCA, respectively. This is the first report of a START domain protein in complex with a sterol ligand. Our original findings indicate that STARD5 may be involved in the transport of bile acids rather than cholesterol. |
| Databáze: | OpenAIRE |
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