4Y9L

Crystal Structure of Caenorhabditis elegans ACDH-11

Summary for 4Y9L

• Entry DOI: 10.2210/pdb4y9l/pdb
• Related: 4Y9J
• Descriptor: Protein ACDH-11, isoform b, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: acyl-coa dehydrogenase, oxidoreductase
• Biological source: Caenorhabditis elegans
• Total number of polymer chains: 2
• Total formula weight: 133251.32

Authors

Li, Z.J.,Zhai, Y.J.,Zhang, K.,Sun, F. (deposition date: 2015-02-17, release date: 2015-06-03, Last modification date: 2023-11-08)

Primary citation

Ma, D.K.,Li, Z.,Lu, A.Y.,Sun, F.,Chen, S.,Rothe, M.,Menzel, R.,Sun, F.,Horvitz, H.R.
Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids
Cell, 161:1152-1163, 2015

PubMed Abstract: Cells adapt to temperature shifts by adjusting levels of lipid desaturation and membrane fluidity. This fundamental process occurs in nearly all forms of life, but its mechanism in eukaryotes is unknown. We discovered that the evolutionarily conserved Caenorhabditis elegans gene acdh-11 (acyl-CoA dehydrogenase [ACDH]) facilitates heat adaptation by regulating the lipid desaturase FAT-7. Human ACDH deficiency causes the most common inherited disorders of fatty acid oxidation, with syndromes that are exacerbated by hyperthermia. Heat upregulates acdh-11 expression to decrease fat-7 expression. We solved the high-resolution crystal structure of ACDH-11 and established the molecular basis of its selective and high-affinity binding to C11/C12-chain fatty acids. ACDH-11 sequesters C11/C12-chain fatty acids and prevents these fatty acids from activating nuclear hormone receptors and driving fat-7 expression. Thus, the ACDH-11 pathway drives heat adaptation by linking temperature shifts to regulation of lipid desaturase levels and membrane fluidity via an unprecedented mode of fatty acid signaling.

PubMed: 25981666
DOI: 10.1016/j.cell.2015.04.026

Experimental method

X-RAY DIFFRACTION (2.27 Å)