Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivity

Structure. 2010 Feb 10;18(2):155-66. doi: 10.1016/j.str.2009.12.012.


A-kinase anchoring proteins (AKAPs) regulate cyclic AMP-dependent protein kinase (PKA) signaling in space and time. Dual-specific AKAP 2 (D-AKAP2) binds to the dimerization/docking (D/D) domain of both RI and RII regulatory subunits of PKA with high affinity. Here we have determined the structures of the RIalpha D/D domain alone and in complex with D-AKAP2. The D/D domain presents an extensive surface for binding through a well-formed N-terminal helix, and this surface restricts the diversity of AKAPs that can interact. The structures also underscore the importance of a redox-sensitive disulfide in affecting AKAP binding. An unexpected shift in the helical register of D-AKAP2 compared to the RIIalpha:D-AKAP2 complex structure makes the mode of binding to RIalpha novel. Finally, the comparison allows us to deduce a molecular explanation for the sequence and spatial determinants of AKAP specificity.

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

  • A Kinase Anchor Proteins / chemistry*
  • A Kinase Anchor Proteins / genetics
  • A Kinase Anchor Proteins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cattle
  • Crystallography, X-Ray
  • Cyclic AMP-Dependent Protein Kinase Type I / chemistry*
  • Cyclic AMP-Dependent Protein Kinase Type I / genetics
  • Cyclic AMP-Dependent Protein Kinase Type I / metabolism*
  • Disulfides / chemistry
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Substrate Specificity


  • A Kinase Anchor Proteins
  • AKAP10 protein, human
  • Disulfides
  • Cyclic AMP-Dependent Protein Kinase Type I

Associated data

  • PDB/3IM3
  • PDB/3IM4