PDBsum entry: 2izy

Transferase

PDB id: 2izy

Contents

Protein chains

47 a.a. *

46 a.a. *

48 a.a. *

Waters ×270

* Residue conservation analysis

PDB id:

2izy

Name:

Transferase

Title:

Molecular basis of akap specificity for pka regulatory subunits

Structure:

Camp-dependent protein kinase regulatory subunit ii. Chain: a, b, c, d, e, f, g, h. Fragment: residues 2-44. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Biol. unit:

Octamer (from PDB file)

Resolution:

2.20Å R-factor: 0.220 R-free: 0.272

Authors:

M.G.Gold,B.Lygren,P.Dokurno,N.Hoshi,G.Mcconnachie,K.Tasken, C.R.Carlson,J.D.Scott,D.Barford

Key ref:

M.G.Gold et al. (2006). Molecular basis of AKAP specificity for PKA regulatory subunits. Mol Cell, 24, 383-395. PubMed id: 17081989 DOI: 10.1016/j.molcel.2006.09.006

Date:

27-Jul-06 Release date: 13-Nov-06

Protein chains

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

Seq: 401 a.a.

Struc: 47 a.a.*

Protein chains

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

Seq: 401 a.a.

Struc: 46 a.a.*

Protein chains

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

Seq: 401 a.a.

Struc: 48 a.a.*

* PDB and UniProt seqs differ at 22 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: 10.1016/j.molcel.2006.09.006

Mol Cell 24:383-395 (2006)

PubMed id: 17081989

Molecular basis of AKAP specificity for PKA regulatory subunits.

M.G.Gold, B.Lygren, P.Dokurno, N.Hoshi, G.McConnachie, K.Taskén, C.R.Carlson, J.D.Scott, D.Barford.

ABSTRACT

Localization of cyclic AMP (cAMP)-dependent protein kinase (PKA) by A kinase-anchoring proteins (AKAPs) restricts the action of this broad specificity kinase. The high-resolution crystal structures of the docking and dimerization (D/D) domain of the RIIalpha regulatory subunit of PKA both in the apo state and in complex with the high-affinity anchoring peptide AKAP-IS explain the molecular basis for AKAP-regulatory subunit recognition. AKAP-IS folds into an amphipathic alpha helix that engages an essentially preformed shallow groove on the surface of the RII dimer D/D domains. Conserved AKAP aliphatic residues dominate interactions to RII at the predominantly hydrophobic interface, whereas polar residues are important in conferring R subunit isoform specificity. Using a peptide screening approach, we have developed SuperAKAP-IS, a peptide that is 10,000-fold more selective for the RII isoform relative to RI and can be used to assess the impact of PKA isoform-selective anchoring on cAMP-responsive events inside cells.

Selected figure(s)

Figure 3.
Figure 3. Core Hydrophobic Interface
(A) Surface representation of the RIIα D/D dimer with AKAP-IS helix shown as ribbons and ball and stick engaged within the AKAP binding groove, view as in Figure 1B.
(B) RII D/D dimer orientation as in (A) showing the antiparallel orientation of the A helices. Aliphatic residues at the AKAP-IS interface are labeled in protomer 1.
(C) View of the hydrophobic ridge of AKAP-IS that interacts with RII. Red-labeled residues are totally buried at the interface.
(D) Ribbon representation of RII D/D and AKAP-IS with side chains of AKAP-IS indicated.

Figure 4.
Figure 4. Details of the AKAP-IS-RIIα D/D Polar Contacts
(A and B) Two detailed views of the interface between AKAP-IS (colored yellow) and αA′ (blue) and αA (magenta) of RII D/D.

The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 24, 383-395) copyright 2006.

Figures were selected by an automated process.