PDBsum entry 4x6q

Transferase

PDB id: 4x6q

Contents

Protein chains

270 a.a.

337 a.a.

Waters ×76

PDB id:

4x6q

Name:

Transferase

Title:

An isoform-specific myristylation switch targets riib pka holoenzymes to membranes

Structure:

Camp-dependent protein kinase type ii-beta regulatory subunit. Chain: b. Engineered: yes. Camp-dependent protein kinase catalytic subunit alpha. Chain: c. Synonym: pka c-alpha. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: prkar2b. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: prkaca, pkaca. Expression_system_taxid: 562

Resolution:

2.52Å R-factor: 0.201 R-free: 0.261

Authors:

P.Zhang,F.Ye,A.C.Bastidas,A.P.Kornev,M.H.Ginsberg,S.S.Taylor

Key ref:

P.Zhang et al. (2015). An Isoform-Specific Myristylation Switch Targets Type II PKA Holoenzymes to Membranes. Structure, 23, 1563-1572. PubMed id: 26278174 DOI: 10.1016/j.str.2015.07.007

Date:

08-Dec-14 Release date: 22-Jul-15

Protein chain

P31324  (KAP3_MOUSE) -  cAMP-dependent protein kinase type II-beta regulatory subunit from Mus musculus

Seq: 416 a.a.

Struc: 270 a.a.*

Protein chain

P05132  (KAPCA_MOUSE) -  cAMP-dependent protein kinase catalytic subunit alpha from Mus musculus

Seq: 351 a.a.

Struc: 337 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain C: E.C.2.7.11.11 - cAMP-dependent protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.str.2015.07.007

Structure 23:1563-1572 (2015)

PubMed id: 26278174

An Isoform-Specific Myristylation Switch Targets Type II PKA Holoenzymes to Membranes.

P.Zhang, F.Ye, A.C.Bastidas, A.P.Kornev, J.Wu, M.H.Ginsberg, S.S.Taylor.

ABSTRACT

Cyclic AMP-dependent protein kinase (PKA) is regulated in part by N-terminal myristylation of its catalytic (C) subunit. Structural information about the role of myristylation in membrane targeting of PKA has been limited. In mammalian cells there are four functionally non-redundant PKA regulatory subunits (RIα, RIβ, RIIα, and RIIβ). PKA is assembled as an inactive R2C2 holoenzyme in cells. To explore the role of N-myristylation in membrane targeting of PKA holoenzymes, we solved crystal structures of RIα:myrC and RIIβ2:myrC2, and showed that the N-terminal myristylation site in the myrC serves as a flexible "switch" that can potentially be mobilized for membrane anchoring of RII, but not RI, holoenzymes. Furthermore, we synthesized nanodiscs and showed by electron microscopy that membrane targeting through the myristic acid is specific for the RII holoenzyme. This membrane-anchoring myristylation switch is independent of A Kinase Anchoring Proteins (AKAPs) that target PKA to membranes by other mechanisms.