Document Detail


Star-related lipid transfer domain protein 5 (STARD5) binds primary bile acids.
MedLine Citation:
PMID:  23018617     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
STeroidogenic Acute Regulatory-related lipid Transfer (START) domain proteins are involved in the non-vesicular 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 (1H-15N-HSQC) approach complemented by circular dichroism and isothermal titration calorimetry were used. Titration of STARD5 with cholic (CA) and chenodeoxycholic acid (CDCA), ligands of the FXR nuclear receptor, leads to drastic perturbation of the 1H-15N-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 1.8.10E4 M(-1) and 6.3.10E4 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.
Authors:
Danny Letourneau; Aurelien Lorin; Andree Lefebvre; Vincent Frappier; Francis Gaudreault; Rafael Najmanovich; Pierre Lavigne; Jean-Guy Lehoux
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-26
Journal Detail:
Title:  Journal of lipid research     Volume:  -     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Universite de Sherbrooke, Canada.
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