3PVB

Crystal structure of (73-244)RIa:C holoenzyme of cAMP-dependent Protein kinase

Summary for 3PVB

• Entry DOI: 10.2210/pdb3pvb/pdb
• Related: 1RGS 2QCS
• Descriptor: cAMP-dependent protein kinase catalytic subunit alpha, cAMP-dependent protein kinase type I-alpha regulatory subunit, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (6 entities in total)
• Functional Keywords: kinase, ria holoenzyme, tetrameric protein kinase a, transferase
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm: P05132; Cell membrane (By similarity): P00514
• Total number of polymer chains: 2
• Total formula weight: 59050.33

Authors

Boettcher, A.J.,Wu, J.,Kim, C.,Yang, J.,Bruystens, J.,Cheung, N.,Pennypacker, J.K.,Blumenthal, D.A.,Kornev, A.P.,Taylor, S.S. (deposition date: 2010-12-06, release date: 2011-02-02, Last modification date: 2024-11-20)

Primary citation

Boettcher, A.J.,Wu, J.,Kim, C.,Yang, J.,Bruystens, J.,Cheung, N.,Pennypacker, J.K.,Blumenthal, D.A.,Kornev, A.P.,Taylor, S.S.
Crystal structure of (73-244)RIa:C holoenzyme of cAMP-dependent Protein kinase
Structure, 19:265-276, 2011

PubMed Abstract: PKA holoenzymes containing two catalytic (C) subunits and a regulatory (R) subunit dimer are activated cooperatively by cAMP. While cooperativity involves the two tandem cAMP binding domains in each R-subunit, additional cooperativity is associated with the tetramer. Of critical importance is the flexible linker in R that contains an inhibitor site (IS). While the IS becomes ordered in the R:C heterodimer, the overall conformation of the tetramer is mediated largely by the N-Linker that connects the D/D domain to the IS. To understand how the N-Linker contributes to assembly of tetrameric holoenzymes, we engineered a monomeric RIα that contains most of the N-Linker, RIα(73-244), and crystallized a holoenzyme complex. Part of the N-linker is now ordered by interactions with a symmetry-related dimer. This complex of two symmetry-related dimers forms a tetramer that reveals novel mechanisms for allosteric regulation and has many features associated with full-length holoenzyme. A model of the tetrameric holoenzyme, based on this structure, is consistent with previous small angle X-ray and neutron scattering data, and is validated with new SAXS data and with an RIα mutation localized to a novel interface unique to the tetramer.

PubMed: 21300294
DOI: 10.1016/j.str.2010.12.005

Experimental method

X-RAY DIFFRACTION (3.3 Å)