Copper(II)-Binding Induces a Unique Polyproline Type II Helical Structure within the Ion-Binding Segment in the Intrinsically Disordered F-Domain of Ecdysteroid Receptor from Aedes aegypti

November 13, 2019

Title

Copper(II)-Binding Induces a Unique Polyproline Type II Helical Structure within the Ion-Binding Segment in the Intrinsically Disordered F-Domain of Ecdysteroid Receptor from Aedes aegypti

Author

Magdalena Rowińska-Żyrek, Anna Wiȩch, Joanna Wa̧tły, Robert Wieczorek, Danuta Witkowska, Andrzej Ożyhar, Marek Orłowski

Year

2019

Journal

Inorganic Chemistry

Abstract

Reproduction of the dominant vector of Zika and dengue diseases, Aedes aegypti mosquito, is controlled by an active heterodimer complex composed of the 20-hydroxyecdysone receptor (EcR) and ultraspiracle protein. Although A. aegypti EcR shares the structural and functional organization with other nuclear receptors, its C-terminus has an additional long F domain (AaFEcR). Recently, we showed that the full length AaFEcR is intrinsically disordered with the ability to specifically bind divalent metal ions. Here, we describe the details of the exhaustive structural and thermodynamic properties of Zn2+- and Cu2+-complexes with the AaFEcR domain, based on peptide models of its two putative metal binding sites (Ac-HGPHPHPHG-NH2 and Ac-QQLTPNQQQHQQQHSQLQQVHANGS-NH2). Unexpectedly, only in the presence of increasing concentrations of Cu2+ ions, the Ac-HGPHPHPHG-NH2 peptide gained a metal ion-induced poly-l-proline type II helical structure, which is unique for members of the family of nuclear receptors.

Instrument

J-1500

Keywords

Circular dichroism, Coordination chemistry, Secondary structure, Chemical stability, Protein folding, Ligand binding, Inorganic chemistry, Biochemistry