5F74

Crystal structure of ChREBP:14-3-3 complex bound with AMP

5F74 の概要

• エントリーDOI: 10.2210/pdb5f74/pdb
• 分子名称: 14-3-3 protein beta/alpha, Carbohydrate-responsive element-binding protein, ADENOSINE MONOPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: chrebp, 14-3-3, amp, allosteric, transcription
• 由来する生物種: Mus musculus (Mouse); 詳細
• 細胞内の位置: Cytoplasm : Q9CQV8; Nucleus : Q8VIP2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51121.63

構造登録者

Jung, H.,Uyeda, K. (登録日: 2015-12-07, 公開日: 2016-03-23, 最終更新日: 2023-09-27)

主引用文献

Sato, S.,Jung, H.,Nakagawa, T.,Pawlosky, R.,Takeshima, T.,Lee, W.R.,Sakiyama, H.,Laxman, S.,Wynn, R.M.,Tu, B.P.,MacMillan, J.B.,De Brabander, J.K.,Veech, R.L.,Uyeda, K.
Metabolite Regulation of Nuclear Localization of Carbohydrate-response Element-binding Protein (ChREBP): ROLE OF AMP AS AN ALLOSTERIC INHIBITOR.
J.Biol.Chem., 291:10515-10527, 2016

PubMed Abstract: The carbohydrate-response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays an essential role in converting excess carbohydrate to fat storage in the liver. In response to glucose levels, ChREBP is regulated by nuclear/cytosol trafficking via interaction with 14-3-3 proteins, CRM-1 (exportin-1 or XPO-1), or importins. Nuclear localization of ChREBP was rapidly inhibited when incubated in branched-chain α-ketoacids, saturated and unsaturated fatty acids, or 5-aminoimidazole-4-carboxamide ribonucleotide. Here, we discovered that protein-free extracts of high fat-fed livers contained, in addition to ketone bodies, a new metabolite, identified as AMP, which specifically activates the interaction between ChREBP and 14-3-3. The crystal structure showed that AMP binds directly to the N terminus of ChREBP-α2 helix. Our results suggest that AMP inhibits the nuclear localization of ChREBP through an allosteric activation of ChREBP/14-3-3 interactions and not by activation of AMPK. AMP and ketone bodies together can therefore inhibit lipogenesis by restricting localization of ChREBP to the cytoplasm during periods of ketosis.

PubMed: 26984404
DOI: 10.1074/jbc.M115.708982

実験手法

X-RAY DIFFRACTION (2.35 Å)