Document Detail


Fatty acids bind tightly to the N-terminal domain of angiopoietin-like protein 4 and modulate its interaction with lipoprotein lipase.
MedLine Citation:
PMID:  22773878     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Angiopoietin-like protein 4 (Angptl4), a potent regulator of plasma triglyceride metabolism, binds to lipoprotein lipase (LPL) through its N-terminal coiled-coil domain (ccd-Angptl4) inducing dissociation of the dimeric enzyme to inactive monomers. In this study, we demonstrate that fatty acids reduce the inactivation of LPL by Angptl4. This was the case both with ccd-Angptl4 and full-length Angptl4, and the effect was seen in human plasma or in the presence of albumin. The effect decreased in the sequence oleic acid > palmitic acid > myristic acid > linoleic acid > linolenic acid. Surface plasmon resonance, isothermal titration calorimetry, fluorescence, and chromatography measurements revealed that fatty acids bind with high affinity to ccd-Angptl4. The interactions were characterized by fast association and slow dissociation rates, indicating formation of stable complexes. The highest affinity for ccd-Angptl4 was detected for oleic acid with a subnanomolar equilibrium dissociation constant (K(d)). The K(d) values for palmitic and myristic acid were in the nanomolar range. Linoleic and linolenic acid bound with much lower affinity. On binding of fatty acids, ccd-Angptl4 underwent conformational changes resulting in a decreased helical content, weakened structural stability, dissociation of oligomers, and altered fluorescence properties of the Trp-38 residue that is located close to the putative LPL-binding region. Based on these results, we propose that fatty acids play an important role in modulating the effects of Angptl4.
Authors:
Terje Robal; Mikael Larsson; Miina Martin; Gunilla Olivecrona; Aivar Lookene
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-07
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-27     Completed Date:  2012-11-19     Revised Date:  2013-08-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29739-52     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Tallinn University of Technology, Tallinn 12618, Estonia.
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MeSH Terms
Descriptor/Qualifier:
Angiopoietins / chemistry,  genetics,  metabolism*
Animals
Binding Sites
Cattle
Fatty Acids / chemistry,  metabolism*
Humans
Lipoprotein Lipase / chemistry,  genetics,  metabolism*
Mice
Plasma / chemistry,  metabolism
Protein Multimerization*
Protein Stability
Protein Structure, Tertiary
Recombinant Proteins / chemistry,  genetics,  metabolism
Serum Albumin / chemistry,  genetics,  metabolism
Substrate Specificity
Surface Plasmon Resonance
Chemical
Reg. No./Substance:
0/ANGPTL4 protein, human; 0/Angiopoietins; 0/Fatty Acids; 0/Recombinant Proteins; 0/Serum Albumin; EC 3.1.1.34/LPL protein, human; EC 3.1.1.34/Lipoprotein Lipase

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


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