Molecular Biology Commons^™

Molecular Mechanism Of Activation-Triggered Subunit Exchange In Human Camkii, M Bhattacharyya, Margaret M. Stratton, Catherine Going, Yongjian Huang, Ethan Mcspadden, Anna Elleman, Pawel Burkhwat, Tiago Barros, Evan Williams, John Kuriyan

Biochemistry & Molecular Biology Department Faculty Publication Series

Activation triggers the exchange of subunits in Ca2+/calmodulin-dependent protein kinase II (CaMKII), an oligomeric enzyme that is critical for learning, memory, and cardiac function. The mechanism by which subunit exchange occurs remains elusive. We show that the human CaMKII holoenzyme exists in dodecameric and tetradecameric forms, and that the calmodulin (CaM)-binding element of CaMKII can bind to the hub of the holoenzyme and destabilize it to release dimers. The structures of CaMKII from two distantly diverged organisms suggest that the CaM-binding element of activated CaMKII acts as a wedge by docking at intersubunit interfaces in the hub. This converts the …