PDBsum entry 4mx3

Signaling protein

PDB id: 4mx3

Contents

Protein chains

272 a.a.

Ligands

CMP ×4

PDB id:

4mx3

Name:

Signaling protein

Title:

Crystal structure of pka rialpha homodimer

Structure:

Camp-dependent protein kinase type i-alpha regulatory subunit. Chain: a, b. Engineered: yes

Source:

Bos taurus. Bovine,cow,domestic cattle,domestic cow. Organism_taxid: 9913. Gene: prkar1a. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.88Å R-factor: 0.261 R-free: 0.287

Authors:

J.G.H.Bruystens,J.Wu,A.Fortezzo,A.P.Kornev,D.A.Blumenthal,S.S.Taylor

Key ref:

J.G.Bruystens et al. (2014). PKA RIα homodimer structure reveals an intermolecular interface with implications for cooperative cAMP binding and Carney complex disease. Structure, 22, 59-69. PubMed id: 24316401 DOI: 10.1016/j.str.2013.10.012

Date:

25-Sep-13 Release date: 15-Jan-14

Protein chains

P00514  (KAP0_BOVIN) -  cAMP-dependent protein kinase type I-alpha regulatory subunit from Bos taurus

Seq: 380 a.a.

Struc: 272 a.a.

DOI no: 10.1016/j.str.2013.10.012

Structure 22:59-69 (2014)

PubMed id: 24316401

PKA RIα homodimer structure reveals an intermolecular interface with implications for cooperative cAMP binding and Carney complex disease.

J.G.Bruystens, J.Wu, A.Fortezzo, A.P.Kornev, D.K.Blumenthal, S.S.Taylor.

ABSTRACT

The regulatory (R) subunit is the cAMP receptor of protein kinase A. Following cAMP binding, the inactive PKA holoenzyme complex separates into two active catalytic (C) subunits and a cAMP-bound R dimer. Thus far, only monomeric R structures have been solved, which fell short in explaining differences of cAMP binding for the full-length protein as compared to the truncated R subunits. Here we solved a full-length R-dimer structure that reflects the biologically relevant conformation, and this structure agrees well with small angle X-ray scattering. An isoform-specific interface is revealed between the protomers. This interface acts as an intermolecular sensor for cAMP and explains the cooperative character of cAMP binding to the RIα dimer. Mutagenesis of residues on this interface not only leads to structural and biochemical changes, but is also linked to Carney complex disease.