Molecular simulations reveal an unresolved conformation of the Type-IA Protein Kinase A regulatory subunit and suggests its role in the cAMP regulatory mechanism

摘要

We identify a previously unresolved, unrecognized, and highly stable conformation of the Protein Kinase A (PKA) regulatory subunit RIα. This conformation, which we refer to as the “Flipback” structure, bridges conflicting characteristics in the crystallographic structures and solution experiments of the PKA RIα heterotetramer. Our simulations reveal a hinge residue in the B/C helix that is conserved through all isoforms of RI. Brownian dynamics simulations suggest that the Flipback conformation plays a role in cAMP association to the A domain of R subunit.