1l6e
From Proteopedia
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Solution structure of the docking and dimerization domain of protein kinase A II-alpha (RIIalpha D/D). Alternatively called the N-terminal dimerization domain of the regulatory subunit of protein kinase A.
Overview
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.
About this Structure
1L6E is a Single protein structure of sequence from Mus musculus. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Tue Nov 20 20:18:49 2007
