General Information on the Regulatory Subunit of Protein Kinase A

The regulatory subunit of protein kinase A, (R), consists of an inhibitor peptide at the N-terminal end that occupies the active site of the catalytic subunit in the holoenzyme form of the protein, keeping the C subunit from phosphorylating any substrate molecules. Two cAMP binding domains, called A and B are also present within the regulatory subunit. When cAMP binds to these sites, the molecule undergoes a conformational change, withdrawing the inhibitor from the C subunit and allowing the R and C subunits to seperate. When cAMP is low, the R subunit reverts to its original conformation and can bind to the C subunit.

The regulatory subunit has only two stable conformations, one in its native tetrameric holoenzyme form (R2C2), and the other with cAMP bound, seperate from the catalytic subunit. As of yet, neither the holoenzyme, nor the natural cAMP-Regulatory complex have had their crystal structures resolved. However, a crystal structure for a mutant of the regulatory subunit bound to cAMP has been elucidated. It is a deletion mutant, with the first 91 amino acid residues at the N-terminus taken out.

The first 21 residues of the mutant protein (91-112)are not seen in the x-ray diffraction and resolution, presumably because it is a disordered region. This region contains the inhibitor peptide that binds to the active site of the catalytic subunit. Since they couldn't be seen, these residues are not shown in the pdb coordinate files. But it is likely that this sequence is either the same or very analogous to the synthetic inhibitor peptide co-crystallized with the catalytic subunit.

Residue 113 is an Arg, which is followed by an alpha-helix (X:N). After this helix ends, domain A starts, and runs for about 100 residues. The carboxyl end domain A is linked directly to the amino side of domain B, which runs another 100 residues.

Above is the structure of the regulatory subunit, with domain A in red, Domain B in blue, cAMP in yellow and the X:N helix in white See the nomenclature section