2QVS

Crystal Structure of Type IIa Holoenzyme of cAMP-dependent Protein Kinase

Summary for 2QVS

• Entry DOI: 10.2210/pdb2qvs/pdb
• Related: 1cx4 1rgs 1u7e
• Descriptor: cAMP-dependent protein kinase, alpha-catalytic subunit, cAMP-dependent protein kinase type II-alpha regulatory subunit (3 entities in total)
• Functional Keywords: camp-dependent protein kinase, type iia holoenzyme, isoform diversity, alternative splicing, atp-binding, cytoplasm, lipoprotein, myristate, nucleotide-binding, nucleus, phosphorylation, serine/threonine-protein kinase, transferase, acetylation, camp-binding, transferase-transferase regulator complex, transferase/transferase regulator
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cytoplasm (By similarity): P05132
• Total number of polymer chains: 2
• Total formula weight: 75958.33

Authors

Wu, J.,Brown, S.H.J.,von Daake, S.,Taylor, S.S. (deposition date: 2007-08-08, release date: 2007-10-23, Last modification date: 2024-10-30)

Primary citation

Wu, J.,Brown, S.H.J.,von Daake, S.,Taylor, S.S.
PKA type IIalpha holoenzyme reveals a combinatorial strategy for isoform diversity.
Science, 318:274-279, 2007

PubMed Abstract: The catalytic (C) subunit of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is inhibited by two classes of regulatory subunits, RI and RII. The RII subunits are substrates as well as inhibitors and do not require adenosine triphosphate (ATP) to form holoenzyme, which distinguishes them from RI subunits. To understand the molecular basis for isoform diversity, we solved the crystal structure of an RIIalpha holoenzyme and compared it to the RIalpha holoenzyme. Unphosphorylated RIIalpha(90-400), a deletion mutant, undergoes major conformational changes as both of the cAMP-binding domains wrap around the C subunit's large lobe. The hallmark of this conformational reorganization is the helix switch in domain A. The C subunit is in an open conformation, and its carboxyl-terminal tail is disordered. This structure demonstrates the conserved and isoform-specific features of RI and RII and the importance of ATP, and also provides a new paradigm for designing isoform-specific activators or antagonists for PKA.

PubMed: 17932298
DOI: 10.1126/science.1146447

Experimental method

X-RAY DIFFRACTION (2.5 Å)