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J Mol Biol. 2006 Mar 3;356(4):1005-13. Epub 2006 Jan 4.

Recombinant human PPAR-beta/delta ligand-binding domain is locked in an activated conformation by endogenous fatty acids.

Author information

1
Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

Abstract

High-resolution crystallographic structures of recombinant human peroxisome proliferator-activated receptor ligand-binding domain (isotype beta/delta) reveal a fatty acid in the binding site. Mass spectrometry confirmed the presence of C16:0, C16:1, C18:0 and C18:1 in a ratio of approximately 3:2:1:4 with 11, Z-octadecenoic acid (cis-vaccenic acid) identified as the predominant species. These are endogenous fatty acids acquired from the bacterial expression system, and serve to lock the ligand-binding domain into the activated conformation. A requirement for crystal growth, the additive n-heptyl-beta-d-glucopyranoside, binds near the activation function helix where recognition of co-activator proteins occurs. Our observations suggest potential physiological ligands for human PPAR-beta/delta and highlight that reported binding studies must be treated with caution unless endogenous fatty acids have been removed from the sample prior to analysis.

PMID:
16405912
DOI:
10.1016/j.jmb.2005.12.047
[Indexed for MEDLINE]

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