文摘
PKA, ubiquitous in mammalian cells, controls many biological processes, and RIa is a major target for diseases associated with PKA signaling. Nonsense-mediated mRNA decay as well as disease mutations in RIα highlight the importance of this holoenzyme for regulating PKA signaling. Mapping these disease mutations reveals clustering at functional hot-spots that define either gain-of-function (CNC) or loss-of-function (ACRDYS) phenotypes. Crystal structure describes one of the dysfunctional ACRDYS mutants with a C-terminal deletion.