Zinc finger protein (ZFP) transcription factors, the largest single class of metalloproteins in the human genome, are  composed of several modular zinc finger domains that contain a single pseudo-tetrahedral Zn(II) binding site.  Typically unfolded in the apo-state, ZFPs undergo metal-induced protein folding events to achieve their biologically active ��a-fold competent for DNA/RNA binding.  Thus, Zn(II) binding, DNA/RNA binding and protein folding are thermodynamically coupled and the precise free energy contribution of Zn(II) towards protein folding and DNA/RNA affinity is poorly understood.  Here, we evaluate the Zn(II) affinity of the fourth zinc finger of the Wilms Tumor Supressor (WT1-4), a Cys2His2 ZFP implicated in pediatric cancer.  Using potentiometry, isothermal titration calorimetry, and equilibrium titrations the conditional dissociation constants have been determined over the pH range of 4.0 � 9.0.  These data reveal the pH independent formation constant, Kf, value and the free energy cost of protein folding in WT1-4.

Zinc(II) binding properties of the fourth zinc finger of the human Wilms tumor suppressor

245th National Meeting (2013)

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