Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium

Nat Struct Mol Biol. 2010 May;17(5):596-601. doi: 10.1038/nsmb.1795. Epub 2010 May 2.

Abstract

Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium binding triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.

Publication types

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

MeSH terms

  • Calcium / chemistry
  • Calcium / metabolism*
  • Cryptosporidium parvum / enzymology*
  • Crystallography, X-Ray
  • Enzyme Activation
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Protein Kinases / chemistry*
  • Protein Kinases / metabolism*
  • Toxoplasma / enzymology*

Substances

  • Protein Kinases
  • calcium-dependent protein kinase
  • Calcium

Associated data

  • PDB/3HX4
  • PDB/3HZT
  • PDB/3IGO
  • PDB/3KU2