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The solution structure of ZNF593 from Homo sapiens reveals a zinc finger in a predominantly unstructured protein. Protein Sci 2008 Mar;17(3):571-6

Date

02/22/2008

Pubmed ID

18287285

Pubmed Central ID

PMC2248319

DOI

10.1110/ps.073290408

Scopus ID

2-s2.0-39549098666   12 Citations

Abstract

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. The tertiary structure of the zinc finger domain is composed of a beta-hairpin that positions the cysteine side chains for zinc coordination, followed by an atypical kinked alpha-helix containing the two histidine side chain ligands. The structural topology of ZNF593 is similar to a fragment of the double-stranded RNA-binding protein Zfa and the C-terminal zinc finger of MBP-1, a human enhancer binding protein. The structure presented here will provide a guide for future functional studies of how ZNF593 negatively modulates the DNA-binding activity of Oct-2, a POU domain-containing transcription factor. Our work illustrates the unique capacity of NMR spectroscopy for structural analysis of folded domains in a predominantly disordered protein.

Author List

Hayes PL, Lytle BL, Volkman BF, Peterson FC

Authors

Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
DNA-Binding Proteins
Humans
Models, Molecular
Molecular Sequence Data
Nuclear Magnetic Resonance, Biomolecular
Sequence Alignment
Solutions
Structural Homology, Protein
Transcription Factors
Zinc Fingers
jenkins-FCD Prod-444 eb4ebd1a08581aba961d3befd3b851a3c3ec6b46