Abstract:  Cell communication is mediated by the formation of protein signaling complexes, where proteins transmit messages through physical interactions, conformational changes, and covalent modifications. The interactions underpinning higher order signaling complexes are characteristically transient to afford rapid responsiveness and reversibility. The physical interactions and associated conformational changes between signaling proteins are the foundations of protein communication. The post synaptic density (PSD) of neurons is composed of a variety of signaling proteins, forming a vast communication network. Pyk2 is a protein kinase in the PSD that is activated via clustering with scaffold protein PSD-95. This clustering releases the autoinhibited conformation of Pyk2, leading to autophosphorylation in trans and subsequent downstream signaling. The structural arrangement and stoichiometries of the PSD-95/Pyk2 complex remain elusive, and the mechanisms of PSD-95 mediated complex assembly remain unclear. The goal of my project is to uncover the structural and regulatory features underlying the Pyk2 and PSD-95 interaction, and probe the conformational dynamics associated with the formation of the Pyk2 activation complex.