4Y9J

Crystal Structure of Caenorhabditis elegans ACDH-11 in complex with C11-CoA

4Y9J の概要

• エントリーDOI: 10.2210/pdb4y9j/pdb
• 関連するPDBエントリー: 4Y9L
• 分子名称: Protein ACDH-11, isoform b, FLAVIN-ADENINE DINUCLEOTIDE, S-{(3S,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5-dioxido-10,14-dioxo-2,4,6-trioxa-11,15-diaza-3lambda~5~,5lambda~5~-diphosphaheptadecan-17-yl} undecanethioate, ... (4 entities in total)
• 機能のキーワード: acyl-coa dehydrogenase, oxidoreductase
• 由来する生物種: Caenorhabditis elegans
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 135122.94

構造登録者

Li, Z.J.,Sun, F. (登録日: 2015-02-17, 公開日: 2015-06-03, 最終更新日: 2024-04-03)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.8 Å)