Structural basis for the transcriptional regulation of membrane lipid homeostasis.

Nature Structural & Molecular Biology
Darcie J MillerS W White

Abstract

DesT is a transcriptional repressor that regulates the genes that control the unsaturated:saturated fatty acid ratio available for membrane lipid synthesis. DesT bound to unsaturated acyl-CoA has a high affinity for its cognate palindromic DNA-binding site, whereas DesT bound to saturated acyl-CoA does not bind this site. Structural analyses of the DesT-oleoyl-CoA-DNA and DesT-palmitoyl-CoA complexes reveal that acyl chain shape directly influences the packing of hydrophobic core residues within the DesT ligand-binding domain. These changes are propagated to the paired DNA-binding domains via conformational changes to modulate DNA binding. These structural interpretations are supported by the in vitro and in vivo characterization of site-directed mutants. The regulation of DesT by the unsaturated:saturated ratio of acyl chains rather than the concentration of a single ligand is a paradigm for understanding transcriptional regulation of membrane lipid homeostasis.

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May 30, 2013·Journal of Agricultural and Food Chemistry·Nazim HussainLixi Jiang
Jul 17, 2012·The Journal of Biological Chemistry·Hitomi SawaiShigetoshi Aono
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Methods Mentioned

BETA
PCR
fluorescence spectroscopy
fluorescence titration

Software Mentioned

Refmac
HOLLOW
PyMol
Resolve
ImageQuant
DesT
Castp
CNS
PROCHECK

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