Molecular dynamics simulations reveal the conformational dynamics of Arabidopsis thaliana BRI1 and BAK1 receptor-like kinases

J Biol Chem. 2017 Jul 28;292(30):12643-12652. doi: 10.1074/jbc.M117.792762. Epub 2017 May 30.

Abstract

The structural motifs responsible for activation and regulation of eukaryotic protein kinases in animals have been studied extensively in recent years, and a coherent picture of their activation mechanisms has begun to emerge. In contrast, non-animal eukaryotic protein kinases are not as well understood from a structural perspective, representing a large knowledge gap. To this end, we investigated the conformational dynamics of two key Arabidopsis thaliana receptor-like kinases, brassinosteroid-insensitive 1 (BRI1) and BRI1-associated kinase 1 (BAK1), through extensive molecular dynamics simulations of their fully phosphorylated kinase domains. Molecular dynamics simulations calculate the motion of each atom in a protein based on classical approximations of interatomic forces, giving researchers insight into protein function at unparalleled spatial and temporal resolutions. We found that in an otherwise "active" BAK1 the αC helix is highly disordered, a hallmark of deactivation, whereas the BRI1 αC helix is moderately disordered and displays swinging behavior similar to numerous animal kinases. An analysis of all known sequences in the A. thaliana kinome found that αC helix disorder may be a common feature of plant kinases.

Keywords: BAK1; BRI1; Markov state models; conformational change; molecular dynamics; plant molecular biology; protein kinase; signal transduction.

MeSH terms

  • Arabidopsis / enzymology*
  • Arabidopsis Proteins / chemistry
  • Arabidopsis Proteins / metabolism*
  • Molecular Dynamics Simulation*
  • Protein Conformation
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / metabolism*

Substances

  • Arabidopsis Proteins
  • Protein Kinases
  • BAK1 protein, Arabidopsis
  • BRI1 protein, Arabidopsis
  • Protein Serine-Threonine Kinases

Associated data

  • PDB/3TL8
  • PDB/4OA2
  • PDB/3UIM
  • PDB/3ULZ
  • PDB/1Y57