A novel target recognition revealed by calmodulin in complex with Ca2+-calmodulin-dependent kinase kinase

Nat Struct Biol. 1999 Sep;6(9):819-24. doi: 10.1038/12271.

Abstract

The structure of calcium-bound calmodulin (Ca2+/CaM) complexed with a 26-residue peptide, corresponding to the CaM-binding domain of rat Ca2+/CaM-dependent protein kinase kinase (CaMKK), has been determined by NMR spectroscopy. In this complex, the CaMKK peptide forms a fold comprising an alpha-helix and a hairpin-like loop whose C-terminus folds back on itself. The binding orientation of this CaMKK peptide by the two CaM domains is opposite to that observed in all other CaM-target complexes determined so far. The N- and C-terminal hydrophobic pockets of Ca2+/CaM anchor Trp 444 and Phe 459 of the CaMKK peptide, respectively. This 14-residue separation between two key hydrophobic groups is also unique among previously determined CaM complexes. The present structure represents a new and distinct class of Ca2+/CaM target recognition that may be shared by other Ca2+/CaM-stimulated proteins.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Binding Sites
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase
  • Calmodulin / chemistry*
  • Calmodulin / genetics
  • Calmodulin / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Serine-Threonine Kinases / chemistry*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Structure, Secondary
  • Rats
  • Sequence Alignment
  • Transfection

Substances

  • Calmodulin
  • Peptide Fragments
  • Protein Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase

Associated data

  • PDB/1CKK