Zinc binding of a Cys2His2-type zinc finger protein is enhanced by the interaction with DNA

書誌事項

公開日
2023-02-23
資源種別
journal article
権利情報
  • https://creativecommons.org/licenses/by/4.0
  • https://creativecommons.org/licenses/by/4.0
DOI
  • 10.1007/s00775-023-01988-1
公開者
Springer Science and Business Media LLC

説明

<jats:sec> <jats:title>Abstract</jats:title> <jats:p>Zinc finger proteins specifically recognize DNA sequences and, therefore, play a crucial role in living organisms. In this study the Zn(II)-, and DNA-binding of 1MEY#, an artificial zinc finger protein consisting of three finger units was characterized by multiple methods. Fluorimetric, circular dichroism and isothermal calorimetric titrations were applied to determine the accurate stability constant of a zinc finger protein. Assuming that all three zinc finger subunits behave identically, the obtained thermodynamic data for the Zn(II) binding were <jats:italic>ΔH</jats:italic><jats:sub>binding site</jats:sub> =  − (23.5 − 28.0) kcal/mol (depending on the applied protonation state of the cysteines) and log<jats:italic>β</jats:italic>’<jats:sub>pH 7.4</jats:sub> = 12.2 ± 0.1, being similar to those of the CP1 consensus zinc finger peptide. The specific DNA binding of the protein can be characterized by log<jats:italic>β</jats:italic>’<jats:sub>pH 7.4</jats:sub> = 8.20 ± 0.08, which is comparable to the affinity of the natural zinc finger proteins (Sp1, WT1, TFIIIA) toward DNA. This value is ~ 1.9 log<jats:italic>β</jats:italic>’ unit higher than those determined for semi- or nonspecific DNA binding. Competitive circular dichroism and electrophoretic mobility shift measurements revealed that the conditional stability constant characteristic for Zn(II) binding of 1MEY# protein increased by 3.4 orders of magnitude in the presence of its target DNA sequence.</jats:p> </jats:sec><jats:sec> <jats:title>Graphical abstract</jats:title> </jats:sec>

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