The third conformation of p38α MAP kinase observed in phosphorylated p38α and in solution

Structure. 2010 Dec 8;18(12):1571-8. doi: 10.1016/j.str.2010.09.015.

Abstract

MAPKs engage substrates, MAP2Ks, and phosphatases via a docking groove in the C-terminal domain of the kinase. Prior crystallographic studies on the unphosphorylated MAPKs p38α and ERK2 defined the docking groove and revealed long-range conformational changes affecting the activation loop and active site of the kinase induced by peptide. Solution NMR data presented here for unphosphorylated p38α with a MEK3b-derived peptide (p38α/pepMEK3b) validate these findings. Crystallograhic data from doubly phosphorylated active p38α (p38α/T∗GY∗/pepMEK3b) reveal a structure similar to unphosphorylated p38α/MEK3b, and distinct from phosphorylated p38γ (p38γ/T∗GY∗) and ERK2 (ERK2/T∗EY∗). The structure supports the idea that MAP kinases adopt three distinct conformations: unphosphorylated, phosphorylated, and a docking peptide-induced form.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Mice
  • Mitogen-Activated Protein Kinase 14 / chemistry*
  • Mitogen-Activated Protein Kinase 14 / isolation & purification
  • Mitogen-Activated Protein Kinase 14 / metabolism*
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Phosphorylation / physiology
  • Protein Binding
  • Protein Interaction Domains and Motifs / physiology
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Solutions

Substances

  • Solutions
  • Mitogen-Activated Protein Kinase 14
  • Mitogen-Activated Protein Kinase Kinases