Heterodimer formation of the myeloid zinc finger 1 SCAN domain and association with promyelocytic leukemia nuclear bodies.

Myeloid zinc finger 1 (MZF1) is a transcription factor that plays an important role in blood cell development. Previous reports indicate MZF1 is an essential factor whose abnormal expression results in cancer. However, the molecular mechanisms by which MZF1 functions in development and contributes to cancer progression remain unknown.

The solution structure of ZNF593 from Homo sapiens reveals a zinc finger in a predominantly unstructured protein.

Here, we report the solution structure of ZNF593, a protein identified in a functional study as a negative modulator of the DNA-binding activity of the Oct-2 transcription factor. ZNF593 contains a classic C(2)H(2) zinc finger domain flanked by about 40 disordered residues on each terminus. Although the protein contains a high degree of intrinsic disorder, the structure of the zinc finger domain was resolved by NMR spectroscopy without a need for N- or C-terminal truncations.

On-column refolding of recombinant chemokines for NMR studies and biological assays.

We have applied an efficient solid-phase protein refolding method to the milligram scale production of natively folded recombinant chemokine proteins. Chemokines are intensely studied proteins because of their roles in immune system regulation, response to inflammation, fetal development, and numerous disease states including, but not limited to, HIV-1/AIDS, cancer metastasis, Crohn's disease, asthma and arthritis. Many investigators use recombinant chemokines for research purposes, however these proteins partition almost exclusively to the inclusion body fraction when produced in Escherichia coli.

Structure of the SCAN domain from the tumor suppressor protein MZF1.

The SCAN domain mediates interactions between members of a subfamily of zinc-finger transcription factors and is found in more than 60 C2H2 zinc finger genes in the human genome, including the tumor suppressor gene myeloid zinc finger 1 (MZF1). Glutathione-S-transferase pull-down assays showed that the MZF1 SCAN domain self-associates, and a Kd value of 600 nM was measured by intrinsic tryptophan fluorescence polarization. The MZF1 structure determined by NMR spectroscopy revealed a domain-swapped dimer.