Neutrons reveal how nature uses structural themes and variation in biological regulation

Healthy cellular function requires tight regulation of a multitude of bio-molecular interactions and processes, often in response to external stimuli. In achieving this regulation, nature uses a number of ‘second messengers’ that are released inside cells in response to first messengers, such as hormones that bind to the cell surface. Divalent calcium and cyclic nucleotides, like cAMP, are among nature's second messengers that bind to receptor proteins inside cells order to regulate the activities of various targets, including many protein kinases. Kinases are enzymes that catalyze the attachment of phosphate groups to proteins in order to modulate their functions. We have been using neutron contrast variation and small-angle solution scattering to study the interactions of the second messenger receptor proteins and their regulatory targets in order to understand the structural basis for these complex processes that use a number of common structural motifs to accomplish highly regulated function. Our most recent work has focused on the different isoforms of the cAMP-dependent protein kinase and the muscle regulatory complex troponin.