PDBsum entry: 1l6e

Transferase

PDB id: 1l6e

Contents

Protein chains

46 a.a. *

* Residue conservation analysis

PDB id:

1l6e

Name:

Transferase

Title:

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.

Structure:

Camp-dependent protein kinase type ii-alpha regulatory chain. Chain: a, b. Fragment: n-terminal docking and dimerization domain. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: riia(1-44). Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

24 models

Authors:

D.Morikis,M.Roy,M.G.Newlon,J.D.Scott,P.A.Jennings

Key ref:

D.Morikis et al. (2002). Electrostatic properties of the structure of the docking and dimerization domain of protein kinase A IIalpha. Eur J Biochem, 269, 2040-2051. PubMed id: 11985580 DOI: 10.1046/j.1432-1033.2002.02852.x

Date:

08-Mar-02 Release date: 03-Apr-02

Protein chains

P12367  (KAP2_MOUSE) -  cAMP-dependent protein kinase type II-alpha regulatory subunit

Seq: 401 a.a.

Struc: 46 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Biological process: signal transduction (1 term)
• Biochemical function: cAMP-dependent protein kinase regulator activity (1 term)

DOI no: 10.1046/j.1432-1033.2002.02852.x

Eur J Biochem 269:2040-2051 (2002)

PubMed id: 11985580

Electrostatic properties of the structure of the docking and dimerization domain of protein kinase A IIalpha.

D.Morikis, M.Roy, M.G.Newlon, J.D.Scott, P.A.Jennings.

ABSTRACT

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.

Selected figure(s)

Figure 4.
Fig. 4. The hydrophobic and electrostatic character of RI D/D.(A) A backbone representation of residues 9–41 of the ensemble of the 24 lowest energy structures of RII D/D. Only side chains of residues with hydrophobic character (Val, Leu, Ile, Phe, Tyr, Thr) are shown (coloured in green). Monomer 1 is coloured in yellow and monomer 2 is coloured in grey. (B) The top view of a van der Waals sphere model of the best (closest to the mean) structure of RII D/D, in an orientation rotated by 90° about the x-axis from the orientation of (A). The colours of the two monomers (yellow and grey) and of the hydrophobic residues (green) are as in (A). The dense hydrophobic face (green atoms) is the binding site of the AKAP peptides. (C) The bottom view of a van der Waals sphere model of the best structure of RII D/D, in an orientation rotated by 180° about the x-axis from the orientation of (B). (D, E, F) Ribbon models of RII D/D (residues -1 to 44) in the same orientation as in (A, B, C), respectively. The view in (D) shows the nearly antiparallel arrangement of helices I, I' and II, II'. Views in (E, F) demonstrate the four-helix bundle structural motif of RII D/D. (G) A backbone representation of RII D/D (residues 9–41), showing the backbone of the monomers 1 (yellow) and 2 (grey) and charged side chains only. Positively charged side chains (Arg, Lys, His) are shown in blue, and negatively charged side chains (Asp, Glu) are shown in red. This view has the same orientation as in (A) and (D). (H) The top view of a van der Waals sphere representation of RII D/D. The orientation of this view is the same as in (B) and (E). (I) The bottom view of a van der Waals sphere representation of RII D/D. The orientation of this view is the same as in (C) and (F), and depicts the highly charged bottom face of RII D/D. Individual panels in this Figure were generated using the program molmol[27].

Figure 6.
Fig. 6. Electrostatic interactions contributing to the stability of RII D/D.(A) Molecular representation of intra-monomer, intra-helical salt bridge between side chains of Arg38 (in blue)–Glu34 (in red), which stabilizes helix II or II' secondary structure. (B) Side chain intra-monomer, inter-helical weak hydrogen bond Tyr35 (in yellow)–Glu19 (in red), which stabilizes tertiary structure. In both (A) (B) only one monomer is shown for clarity, with helix I drawn in cyan and helix II drawn in magenta. (C) Inter-monomer hydrogen bond between side chains of Arg40 (in blue)–Asp30 (in red), which stabilizes quaternary structure. The two monomers are drawn in yellow and green, respectively. Only one pair of Arg40-Asp30 is shown for clarity.

The above figures are reprinted by permission from the Federation of European Biochemical Societies: Eur J Biochem (2002, 269, 2040-2051) copyright 2002.

Figures were selected by an automated process.