4GFX

Crystal structure of the N-terminal domain of TXNIP

4GFX の概要

• エントリーDOI: 10.2210/pdb4gfx/pdb
• 分子名称: Thioredoxin-interacting protein, GLYCEROL (3 entities in total)
• 機能のキーワード: arrestin-like fold, protein binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): Q9H3M7
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17149.59

構造登録者

Hwang, J.,Kim, M.H. (登録日: 2012-08-04, 公開日: 2014-02-05, 最終更新日: 2024-11-06)

主引用文献

Hwang, J.,Suh, H.W.,Jeon, Y.H.,Hwang, E.,Nguyen, L.T.,Yeom, J.,Lee, S.G.,Lee, C.,Kim, K.J.,Kang, B.S.,Jeong, J.O.,Oh, T.K.,Choi, I.,Lee, J.O.,Kim, M.H.
The structural basis for the negative regulation of thioredoxin by thioredoxin-interacting protein.
Nat Commun, 5:2958-2958, 2014

PubMed Abstract: The redox-dependent inhibition of thioredoxin (TRX) by thioredoxin-interacting protein (TXNIP) plays a pivotal role in various cancers and metabolic syndromes. However, the molecular mechanism of this regulation is largely unknown. Here, we present the crystal structure of the TRX-TXNIP complex and demonstrate that the inhibition of TRX by TXNIP is mediated by an intermolecular disulphide interaction resulting from a novel disulphide bond-switching mechanism. Upon binding to TRX, TXNIP undergoes a structural rearrangement that involves switching of a head-to-tail interprotomer Cys63-Cys247 disulphide between TXNIP molecules to an interdomain Cys63-Cys190 disulphide, and the formation of a de novo intermolecular TXNIP Cys247-TRX Cys32 disulphide. This disulphide-switching event unexpectedly results in a domain arrangement of TXNIP that is entirely different from those of other arrestin family proteins. We further show that the intermolecular disulphide bond between TRX and TXNIP dissociates in the presence of high concentrations of reactive oxygen species. This study provides insight into TRX and TXNIP-dependent cellular regulation.

PubMed: 24389582
DOI: 10.1038/ncomms3958

実験手法

X-RAY DIFFRACTION (1.6 Å)