The Combinatorial Extension Method Reveals a Sphingolipid Binding Domain on Pancreatic Bile Salt-Dependent Lipase: Role in Secretion

Structure similarity searches using a combinatorial extension appoach revealed that a protein fold structurally related to the sphingolipid binding domain (SBD) of HIV-1 gp120 (V3 loop) is present on pancreatic bile salt-dependent lipase (BSDL). A synthetic peptide derived from the predicted V3-like...

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Bibliographic Details
Published in:Structure (London) 2004-08, Vol.12 (8), p.1437-1447
Main Authors: Aubert-Jousset, Emeline, Garmy, Nicolas, Sbarra, Véronique, Fantini, Jacques, Sadoulet, Marie-Odile, Lombardo, Dominique
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Bridged-Ring Compounds - pharmacology
Caveolin 1
Caveolins - metabolism
CHO Cells
Cloning, Molecular
Cricetinae
Cricetulus
Exocytosis - drug effects
Exocytosis - physiology
Filipin - pharmacology
HIV Envelope Protein gp120 - genetics
Human immunodeficiency virus 1
Membrane Microdomains - metabolism
Models, Molecular
Molecular Sequence Data
Morpholines - pharmacology
Phosphorylation - drug effects
Protein Folding
Rats
Sphingolipids - chemistry
Sterol Esterase - genetics
Sterol Esterase - metabolism
Sterol Esterase - secretion
Thiones - pharmacology
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Summary:Structure similarity searches using a combinatorial extension appoach revealed that a protein fold structurally related to the sphingolipid binding domain (SBD) of HIV-1 gp120 (V3 loop) is present on pancreatic bile salt-dependent lipase (BSDL). A synthetic peptide derived from the predicted V3-like domain of BSDL interacted with reconstituted monolayers of sphingolipids such as GalCer and GlcCer. Using Chinese hamster ovary cells stably transfected with the cDNA encoding the rat BSDL (CHO-3B clone) or pancreatic SOJ-6 cells expressing the human BSDL as models, we showed that the enzyme cofractionates with caveolin-1. The secretion of BSDL by CHO-3B cells was inhibited by permeable drugs affecting rafts structure (D609, PDMP, and filipin). Data suggest that the functional interaction between the BSDL SBD and lipid rafts is physiologically relevant and could be essential for sensing the BSDL folding prior to secretion. A tentative model accounting for the phosphorylation-induced dissociation of BSDL from rafts is presented.
ISSN:0969-2126
1878-4186
DOI:10.1016/j.str.2004.05.016