Premium
Conformational regulation of the C‐terminal random coil in S100A4 by Ca2+ ions
Author(s) -
Katona Gergely,
Duelli Annette,
Kiss Bence,
Lundholm Ida,
Bodor Andrea,
Petoukhov Maxim,
Svergun Dmitri,
Nyitray Laszlo
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.563.5
Subject(s) - random coil , isothermal titration calorimetry , terminal (telecommunication) , chemistry , crystallography , mutant , biophysics , wild type , coiled coil , circular dichroism , biochemistry , biology , gene , telecommunications , computer science
S100A4 or metastasin plays a central role in the progression of metastatic diseases. Like many other examples, the protein S100A4 contains ordered and disordered regions. The aim of this study was to determine how the disordered C‐terminal region influences the binding to Ca2+ and in turn how Ca 2+ binding alters the dynamics of the C‐terminal random coil. The combination of small angle X‐ray scattering, pulsed field gradient NMR measurements revealed a conformational change upon binding in the wild‐type protein, but not in the C‐terminal deleted mutant. Comparative isothermal titration calorimetry measurements also indicated that Ca 2+ ions bind more tightly to the C‐terminal deleted mutant than the wild‐type protein. Molecular dynamics simulations provide a rational: in the wild type protein the positively charged C‐terminal random coil region interacts strongly with the EF hand residues when they do not coordinate Ca 2+ , whereas the C‐terminal region is more free to move in the Ca 2+ ‐bound form of the protein. The C‐terminal random coil never appear to be completely static, but occupies a different conformational space depending on the functional state of is Ca 2+ binding protein. Thus this study provides a unique insight to the regulation of random coil regions.