Structure of the N-terminal domain of human thioredoxin-interacting protein

Galina Polekhina, David B Ascher, Shie Foong Kok, Simone Alexandra Beckham, Matthew Charles James Wilce, Mark Waltham

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

Abstract

Thioredoxin-interacting protein (TXNIP) is one of the six known alpha-arrestins and has recently received considerable attention owing to its involvement in redox signalling and metabolism. Various stress stimuli such as high glucose, heat shock, UV, H2O2 and mechanical stress among others robustly induce the expression of TXNIP, resulting in the sequestration and inactivation of thioredoxin, which in turn leads to cellular oxidative stress. While TXNIP is the only alpha-arrestin known to bind thioredoxin, TXNIP and two other alpha-arrestins, Arrdc4 and Arrdc3, have been implicated in metabolism. Furthermore, owing to its roles in the pathologies of diabetes and cardiovascular disease, TXNIP is considered to be a promising drug target. Based on their amino-acid sequences, TXNIP and the other alpha-arrestins are remotely related to beta-arrestins. Here, the crystal structure of the N-terminal domain of TXNIP is reported. It provides the first structural information on any of the alpha-arrestins and reveals that although TXNIP adopts a beta-arrestin fold as predicted, it is structurally more similar to Vps26 proteins than to beta-arrestins, while sharing below 15 pairwise sequence identity with either.
Original languageEnglish
Pages (from-to)333 - 344
Number of pages12
JournalActa Crystallographica Section D: Biological Crystallography
Volume69
Issue number3
DOIs
Publication statusPublished - 2013

Cite this