Journal
STRUCTURE
Volume 22, Issue 1, Pages 59-69Publisher
CELL PRESS
DOI: 10.1016/j.str.2013.10.012
Keywords
-
Funding
- NIH [GM 034921]
- San Diego Fellowship
- Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]
- US Department of Energy [DE-FG02-05ER64026]
Ask authors/readers for more resources
The regulatory (R) subunit is the cAMP receptor of protein kinase A. Following cAMP binding, the inactive PKA holoenzyme complex separates into two active catalytic (C) subunits and a cAMP-bound R dimer. Thus far, only monomeric R structures have been solved, which fell short in explaining differences of cAMP binding for the full-length protein as compared to the truncated R subunits. Here we solved a full-length R-dimer structure that reflects the biologically relevant conformation, and this structure agrees well with small angle X-ray scattering. An isoform-specific interface is revealed between the protomers. This interface acts as an intermolecular sensor for cAMP and explains the cooperative character of cAMP binding to the Riot dimer. Mutagenesis of residues on this interface not only leads to structural and biochemical changes, but is also linked to Carney complex disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available