The molecular basis for protein kinase A anchoring revealed by solution
NMR
Marceen Glavic Newlon1, Melinda Roy1, Dimitrios Morikis1, Zachary E. Hausken2, Vincent Coghlan3, John D. Scott2
& Patricia A. Jennings1
1
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0359.
2
Howard Hughes Medical Institute, Vollum Institute, Portland, Oregon 97201-3098.
3
R.S. Dow Neurological Sciences Institute, Oregon Health Sciences University, Portland, Oregon 97209-1595.
Correspondence should be addressed to Patricia A. Jennings pajennin@ucsd.edu
Compartmentalization of signal transduction enzymes into signaling complexes
is an important mechanism to ensure the specificity of intracellular events.
Formation of these complexes is mediated by specialized protein motifs that
participate in protein−protein interactions. The adenosine 3´,5´-cyclic
monophosphate (cAMP)-dependent protein kinase (PKA) is localized through interaction
of the regulatory (R) subunit dimer with A-kinase-anchoring proteins (AKAPs).
We now report the solution structure of the type II PKA R-subunit fragment
RII(1−44), which encompasses both the AKAP-binding and dimerization
interfaces. This structure incorporates an X-type four-helix bundle dimerization
motif with an extended hydrophobic face that is necessary for high-affinity
AKAP binding. NMR data on the complex between RII(1−44) and an
AKAP fragment reveals extensive contacts between the two proteins. Interestingly,
this same dimerization motif is present in other signaling molecules, the
S100 family. Therefore, the X-type four-helix bundle may represent a conserved
fold for protein−protein interactions in signal transduction.
(1−44), which encompasses both the AKAP-binding and dimerization
interfaces. This structure incorporates an X-type four-helix bundle dimerization
motif with an extended hydrophobic face that is necessary for high-affinity
AKAP binding. NMR data on the complex between RII
