2qcs
From Proteopedia
A complex structure between the Catalytic and Regulatory subunit of Protein Kinase A that represents the inhibited state
Overview
Protein kinase A (PKA) holoenzyme is one of the major receptors for cyclic adenosine monophosphate (cAMP), where an extracellular stimulus is translated into a signaling response. We report here the structure of a complex between the PKA catalytic subunit and a mutant RI regulatory subunit, RIalpha(91-379:R333K), containing both cAMP-binding domains. Upon binding to the catalytic subunit, RI undergoes a dramatic conformational change in which the two cAMP-binding domains uncouple and wrap around the large lobe of the catalytic subunit. This large conformational reorganization reveals the concerted mechanism required to bind and inhibit the catalytic subunit. The structure also reveals a holoenzyme-specific salt bridge between two conserved residues, Glu261 and Arg366, that tethers the two adenine capping residues far from their cAMP-binding sites. Mutagenesis of these residues demonstrates their importance for PKA activation. Our structural insights, combined with the mutagenesis results, provide a molecular mechanism for the ordered and cooperative activation of PKA by cAMP.
About this Structure
2QCS is a Protein complex structure of sequences from Bos taurus and Mus musculus. Full crystallographic information is available from OCA.
Reference
PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation., Kim C, Cheng CY, Saldanha SA, Taylor SS, Cell. 2007 Sep 21;130(6):1032-43. PMID:17889648 Page seeded by OCA on Sun May 4 14:44:38 2008
Categories: Bos taurus | Mus musculus | Protein complex | CAMP-dependent protein kinase | Cheng, C Y. | Kim, C. | Saldanha, A S. | Taylor, S S. | Camp-dependent protein kinase | Conformational change | Cyclic adenosine monophosphate | Cyclic nucleotide binding domain | Pka holoenzyme | Protein binding | Protein-protein interaction | Transferase/transferase inhibitor complex
