| Structural highlights
1l6e is a 2 chain structure with sequence from Lk3 transgenic mice. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 1r2a |
| Gene: | RIIA(1-44) (LK3 transgenic mice) |
| Activity: | Transferase, with EC number 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
Function
[KAP2_MOUSE] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The structure of the N-terminal docking and dimerization domain of the type IIalpha regulatory subunit (RIIalpha D/D) of protein kinase A (PKA) forms a noncovalent stand-alone X-type four-helix bundle structural motif, consisting of two helix-loop-helix monomers. RIIalpha D/D possesses a strong hydrophobic core and two distinct, exposed faces. A hydrophobic face with a groove is the site of protein-protein interactions necessary for subcellular localization. A highly charged face, opposite to the former, may be involved in regulation of protein-protein interactions as a result of changes in phosphorylation state of the regulatory subunit. Although recent studies have addressed the hydrophobic character of packing of RIIalpha D/D and revealed the function of the hydrophobic face as the binding site to A-kinase anchoring proteins (AKAPs), little attention has been paid to the charges involved in structure and function. To examine the electrostatic character of the structure of RIIalpha D/D we have predicted mean apparent pKa values, based on Poisson-Boltzmann electrostatic calculations, using an ensemble of calculated dimer structures. We propose that the helix promoting sequence Glu34-X-X-X-Arg38 stabilizes the second helix of each monomer, through the formation of a (i, i +4) side chain salt bridge. We show that a weak inter-helical hydrogen bond between Tyr35-Glu19 of each monomer contributes to tertiary packing and may be responsible for discriminating from alternative quaternary packing of the two monomers. We also show that an inter-monomer hydrogen bond between Asp30-Arg40 contributes to quaternary packing. We propose that the charged face comprising of Asp27-Asp30-Glu34-Arg38-Arg40-Glu41-Arg43-Arg44 may be necessary to provide flexibility or stability in the region between the C-terminus and the interdomain/autoinhibitory sequence of RIIalpha, depending on the activation state of PKA. We also discuss the structural requirements necessary for the formation of a stacked (rather than intertwined) dimer, which has consequences for the orientation of the functionally important and distinct faces.
Electrostatic properties of the structure of the docking and dimerization domain of protein kinase A IIalpha.,Morikis D, Roy M, Newlon MG, Scott JD, Jennings PA Eur J Biochem. 2002 Apr;269(8):2040-51. PMID:11985580[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Morikis D, Roy M, Newlon MG, Scott JD, Jennings PA. Electrostatic properties of the structure of the docking and dimerization domain of protein kinase A IIalpha. Eur J Biochem. 2002 Apr;269(8):2040-51. PMID:11985580
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