Crystallization and preliminary X-ray analysis of the N-terminal domain of human thioredoxin-interacting protein

Galina Polekhina, David Ascher, Shie Kok, Mark Waltham

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Thioredoxin-interacting protein (TXNIP) is a negative regulator of thioredoxin and its roles in the pathologies of diabetes and cardiovascular diseases have marked it out as a potential drug target. Expression of TXNIP is robustly induced under various stress conditions such as high glucose, heat shock, UV, H(2)O(2) and mechanical stress amongst others. Elevated levels of TXNIP result in the sequestration and inactivation of thioredoxin, leading to cellular oxidative stress. For some time, this was the only known function of TXNIP; however, more recently the protein has been shown to play a role in regulation of glucose uptake and activation of the inflammasome. Based on the primary sequence, TXNIP is remotely related to beta-arrestins, which include the visual arrestins. TXNIP has thus been classified as a member of the alpha-arrestin family, which to date includes five other members. None of the other alpha-arrestins are known to interact with thioredoxin, although curiously one has been implicated in glucose uptake. In order to gain insight into the structure-function relationships of the alpha-arrestin protein family, and particularly that of TXNIP, the N-terminal domain of TXNIP has been crystallized. The crystals belonged to a monoclinic space group and diffracted to 3 A resolution using synchrotron radiation.
Original languageEnglish
Pages (from-to)613 - 617
Number of pages5
Journal Acta Crystallographica Section F: Structural Biology Communications
Volume67
Issue numberPt 5
DOIs
Publication statusPublished - 2011

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