PDBsum entry: 1r2a

Transferase

PDB id: 1r2a

Contents

Protein chains

46 a.a. *

* Residue conservation analysis

PDB id:

1r2a

Name:

Transferase

Title:

The molecular basis for protein kinase a anchoring revealed by solution nmr

Structure:

Protein (camp-dependent protein kinase type ii regulatory subunit). Chain: a, b. Fragment: dimerization-anchoring domain. Synonym: riia(1-44). Engineered: yes

Source:

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

NMR struc:

17 models

Authors:

M.G.Newlon,M.Roy,D.Morikis,Z.E.Hausken,V.Coghlan,J.D.Scott, P.A.Jennings

Key ref:

M.G.Newlon et al. (1999). The molecular basis for protein kinase A anchoring revealed by solution NMR. Nat Struct Biol, 6, 222-227. PubMed id: 10074940 DOI: 10.1038/6663

Date:

07-Dec-98 Release date: 16-Dec-98

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: 10.1038/6663

Nat Struct Biol 6:222-227 (1999)

PubMed id: 10074940

The molecular basis for protein kinase A anchoring revealed by solution NMR.

M.G.Newlon, M.Roy, D.Morikis, Z.E.Hausken, V.Coghlan, J.D.Scott, P.A.Jennings.

ABSTRACT

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 RIIalpha(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 RIIalpha(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.

Selected figure(s)

Figure 2.
Figure 2. Backbone fold and protomer orientation of RII (1−44). a, Stereo views of the best-fit superposition of the 17 lowest energy structures of RII (1−44) dimer generated in X-PLOR 3.851^13, ^17. The independent protomers are colored in red and blue, respectively. b, This view highlights the alternate antiparallel packing of helices in the X-type four-helix bundle^19. c, A schematic diagram of RII (1−44) emphasizing the antiparallel arrangement of the chains in the dimer. The independent protomers are colored in blue and red, respectively. Residues that form disordered regions, turns and -helices are shown in the open, lightly shaded and closed circles, respectively. Subdomain I is formed from helices I and I', while subdomain II is formed from helices II and II'.

Figure 3.
Figure 3. Representations of the surface potential and hydrophobic core of RII (1−44). a, An electrostatic surface representation of RII (1−44) with acidic and basic regions represented in red and blue, respectively^31. The hydrophobic face and putative AKAP-binding crevice are readily apparent in this representation. This view is of the surface made from the antiparallel packing of helices I and Í and is a 90° rotation from the view presented in Fig. 2b. b, This view is of the highly charged surface made from the antiparallel packing of helices II and IÍ. This latter view is generated by a 180^° rotation from Fig. 3a. c, View of a superposition of the 17 best structures of RII (1−44) using MOLMOL^31 highlighting only the hydrophobic residues, which are colored in green. The two protomers in the dimer are colored yellow and white, respectively. The N-terminal eight residues are deleted in this representation for clarity.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 222-227) copyright 1999.

Figures were selected by an automated process.