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CamKII Kinase Research

Calcium/Calmodulin dependent Protein Kinase II (CaMKII) is highly expressed in and modulates numerous aspects of neuronal function. This is accomplished through a variety of mechanisms including influencing signaling pathways, modulating neurotransmitter and ion channel function, neurotransmitter synthesis, cytoskeletal interactions, and gene expression. Inhibition of CaMKII may offer methods for treatment of diseases with excitatory synaptic transmission abnormalities such as cardiac arrhythmias, cardiomyopathy, and Parkinson’s disease. It is therefore essential to understand the structure and dynamics of CaMKII in order to identify possible approaches to inhibition.

CaMKII exists in a dodecameric assembly consisting of two stacked hexameric rings. Each individual subunit has its own catalytic activity and can activate neighboring subunits in the presence of Ca2+/calmodulin. Using EPR and biochemical techniques we aim to decipher the structural mechanism by which CaMKII is activated by calmodulin. It is important to understand activation both in individual subunits and within the context of the holoenzyme.

Current Researchers
Laurel Hoffman, Graduate Student.My research aim is to to develop a structure based activation mechanism of CaMKII using spectroscopy.
Recent Publications
Hoffman L, Stein RA, Colbran RJ, Mchaourab HS. Conformational changes underlying calcium/calmodulin-dependent protein kinase II activation. EMBO J. 2011 Apr 6;30(7):1251-62. PMID: 21343908.