Functional characterisation of ganglioside-induced differentiation-associated protein 1 as a glutathione transferase

Alison J. Shield, Tracy P. Murray, Philip G. Board*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    53 Citations (Scopus)

    Abstract

    Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene have been linked with Charcot-Marie-Tooth (CMT) disease. This protein, and its paralogue GDAP1L1, appear to be structurally related to the cytosolic glutathione S-transferases (GST) including an N-terminal thioredoxin fold domain with conserved active site residues. The specific function, of GDAP1 remains unknown. To further characterise their structure and function we purified recombinant human GDAP1 and GDAP1L1 proteins using bacterial expression and immobilised metal affinity chromatography. Like other cytosolic GSTs, GDAP1 protein has a dimeric structure. Although the full-length proteins were largely insoluble, the deletion of a proposed C-terminal transmembrane domain allowed the preparation of soluble protein. The purified proteins were assayed for glutathione-dependent activity against a library of 'prototypic' GST substrates. No evidence of glutathione-dependent activity or an ability to bind glutathione immobilised on agarose was found.

    Original languageEnglish
    Pages (from-to)859-866
    Number of pages8
    JournalBiochemical and Biophysical Research Communications
    Volume347
    Issue number4
    DOIs
    Publication statusPublished - 8 Sept 2006

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