Ensemble structural analyses depict the regulatory mechanism of non-phosphorylated human MAP2K4

Biochem Biophys Res Commun. 2020 Jan 1;521(1):106-112. doi: 10.1016/j.bbrc.2019.10.086. Epub 2019 Oct 18.

Abstract

Mitogen-activated protein kinase kinase 4 (MAP2K4) plays a critical role in regulating the stress-activated protein kinase signaling cascade. A small angle X-ray scattering experiment, a powerful technique for analyzing a solution structure cleared from the structural artifacts due to crystal packing, provided the ensemble structures of human non-phosphorylated MAP2K4 in three states involving the apo form, the binary complex with an ATP analogue, and the ternary complex with the ATP analogue and substrate peptide. These ensemble structures provided more detailed mechanisms for regulating MAP2K4 in addition to those delineated only by the crystal structures in three states.

Keywords: Ensemble optimization method; MAP2K4; Molecular fluctuation; Regulatory mechanism; Small angle X-ray scattering.

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism
  • Humans
  • MAP Kinase Kinase 4 / analysis*
  • MAP Kinase Kinase 4 / metabolism*
  • Protein Conformation
  • Scattering, Small Angle
  • X-Ray Diffraction

Substances

  • Adenosine Triphosphate
  • MAP Kinase Kinase 4
  • MAP2K4 protein, human