title: Crystallization and preliminary X-ray analysis of the N-terminal domain of human thioredoxin-interacting protein.
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 β-arrestins, which include the visual arrestins. TXNIP has thus been classified as a member of the α-arrestin family, which to date includes five other members. None of the other α-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 α-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 Å resolution using synchrotron radiation.
authors.affiliation: Structural Biology, Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, Victoria 3168, Australia. galina.polekhina@monash.edu
authors.forename: Galina
authors.initials: G
authors.lastname: Polekhina
authors.forename: David Benjamin
authors.initials: DB
authors.lastname: Ascher
authors.forename: Shie Foong
authors.initials: SF
authors.lastname: Kok
authors.forename: Mark
authors.initials: M
authors.lastname: Waltham
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D006801:Humans
chemical_list: D002352:Carrier Proteins; C486715:TXNIP protein, human