Journal of Biological Chemistry
Volume 279, Issue 38, 17 September 2004, Pages 39789-39797
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Protein Structure and Folding
A Classic Zinc Finger from Friend of GATA Mediates an Interaction with the Coiled-coil of Transforming Acidic Coiled-coil 3*

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Classic zinc finger domains (cZFs) consist of a β-hairpin followed by an α-helix. They are among the most abundant of all protein domains and are often found in tandem arrays in DNA-binding proteins, with each finger contributing an α-helix to effect sequence-specific DNA recognition. Lone cZFs, not found in tandem arrays, have been postulated to function in protein interactions. We have studied the transcriptional co-regulator Friend of GATA (FOG), which contains nine zinc fingers. We have discovered that the third cZF of FOG contacts a coiled-coil domain in the centrosomal protein transforming acidic coiled-coil 3 (TACC3). Although FOG-ZF3 exhibited low solubility, we have used a combination of mutational mapping and protein engineering to generate a derivative that was suitable for in vitro and structural analysis. We report that the α-helix of FOG-ZF3 recognizes a C-terminal portion of the TACC3 coiled-coil. Remarkably, the α-helical surface utilized by FOG-ZF3 is the same surface responsible for the well established sequence-specific DNA-binding properties of many other cZFs. Our data demonstrate the versatility of cZFs and have implications for the analysis of many as yet uncharacterized cZF proteins.

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The atomic coordinates and structure factors (code 1srk) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

*

This work was supported in part by grants from the Australian Research Council (ARC) and the Australian National Health and Medical Research Council (NHMRC). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§

Both authors contributed equally to this work.

Supported by an Australian Postgraduate Award.

**

An ARC Australian Research Fellow.