That zincing feeling: the effects of EDTA on the behaviour of zinc-binding transcriptional regulators.
Zinc-binding proteins account for nearly half of the transcription regulatory proteins in the human genome and are the most abundant class of proteins in the human proteome. The zinc-binding transcriptional regulatory proteins utilize Zn2+ to fold structural domains that participate in intermolecular interactions. A study by Matt et al. in this issue of the Biochemical Journal has examined the transcription factor binding properties of the zinc-binding module C/H1 (cysteine/histidine-rich region 1) found in the transcriptional co-activator proteins CBP (CREB-binding protein) and p300. Their studies revealed that EDTA treatment of native C/H1 leads to irreversible denaturation and aggregation. Of particular concern is their finding that unfolded C/H1 participates in non-specific protein-protein interactions. The implications of these results are significant. EDTA is a very potent zinc-chelating agent that is used ubiquitously in protein interaction studies and in molecular biology in general. The potentially detrimental effects of EDTA on the structure and interactions of zinc-binding proteins should be taken into account in the interpretation of a sizeable number of published studies and must be considered in future experiments.
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, USA. Jennifer.Nyborg@colostate.edu
Jennifer K
JK
Nyborg
Olve B
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Peersen
D000818:Animals; D004492:Edetic Acid / Q000494:pharmacology*; D006801:Humans; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015032:Zinc / Q000378:metabolism*; D016335:Zinc Fingers / Q000187:drug effects / Q000502:physiology
D014157:Transcription Factors; D004492:Edetic Acid; D015032:Zinc