Document Detail

StAR-related lipid transfer domain protein 5 binds primary bile acids.
MedLine Citation:
PMID:  23018617     Owner:  NLM     Status:  MEDLINE    
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.
Danny Létourneau; Aurélien Lorin; Andrée Lefebvre; Vincent Frappier; Francis Gaudreault; Rafael Najmanovich; Pierre Lavigne; Jean-Guy LeHoux
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-09-26
Journal Detail:
Title:  Journal of lipid research     Volume:  53     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-09     Completed Date:  2013-04-25     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2677-89     Citation Subset:  IM    
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MeSH Terms
Binding Sites
Carrier Proteins / chemistry*,  genetics,  isolation & purification
Chenodeoxycholic Acid / chemistry*
Cholic Acid / chemistry*
Cloning, Molecular
Magnetic Resonance Spectroscopy / standards
Models, Molecular
Protein Stability
Reference Standards
Structure-Activity Relationship
Grant Support
MT-10983//Canadian Institutes of Health Research
Reg. No./Substance:
0/Carrier Proteins; 0/Ligands; 0/STARD5 protein, human; 0GEI24LG0J/Chenodeoxycholic Acid; G1JO7801AE/Cholic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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