3J4R: Pseudo-atomic Model Of The Akap18-pka Complex In A Linear Conformation Derived From Electron Microscopy

Citation:
Abstract
Anchoring proteins sequester kinases with their substrates to locally disseminate intracellular signals and avert indiscriminate transmission of these responses throughout the cell. Mechanistic understanding of this process is hampered by limited structural information on these macromolecular complexes. A-kinase anchoring proteins (AKAPs) spatially constrain phosphorylation by cAMP-dependent protein kinases (PKA). Electron microscopy and three-dimensional reconstructions of type-II PKA-AKAP18gamma complexes reveal hetero-pentameric assemblies that adopt a range of flexible tripartite configurations. Intrinsically disordered regions within each PKA regulatory subunit impart the molecular plasticity that affords an approximately 16 nanometer radius of motion to the associated catalytic subunits. Manipulating flexibility within the PKA holoenzyme augmented basal and cAMP responsive phosphorylation of AKAP-associated substrates. Cell-based analyses suggest that the catalytic subunit remains within type-II PKA-AKAP18gamma complexes upon cAMP elevation. We propose that the dynamic movement of kinase sub-structures, in concert with the static AKAP-regulatory subunit interface, generates a solid-state signaling microenvironment for substrate phosphorylation. DOI: http://dx.doi.org/10.7554/eLife.01319.001.
PDB ID: 3J4RDownload
MMDB ID: 115003
PDB Deposition Date: 2013/9/25
Updated in MMDB: 2013/11
Experimental Method:
electron microscopy
Resolution: 35  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 3J4R: pentameric; determined by author
Molecular Components in 3J4R
Label Count Molecule
Proteins (5 molecules)
1
A-kinase Anchor Protein 18
Molecule annotation
2
Camp-dependent Protein Kinase Type Ii-alpha Regulatory Subunit
Molecule annotation
2
Camp-dependent Protein Kinase Catalytic Subunit Alpha(Gene symbol: Prkaca)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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