Voltage-gated ion channels are membrane proteins that generate fast electrical signals in excitable tissue. They are responsible for the heartbeat, the neural impulse, and for triggering chemical secretion and muscle contraction. In response to changes in membrane voltage these channels open and close.molecular gates that control the flow of ions across the membrane. The voltage sensor of the channel is known to be a charged protein segment that is pushed through the membrane by voltage. The exact nature of this protein motion, its mechanism of regulation, and the way that it opens and closes the gates are not known. Nor is it known how the gates interact and how this process is modulated by interaction with auxiliary proteins. We address these questions, and we focus on one of these auxiliary proteins, which is a member of a family of regulatory enzymes called reductases. We ask not only how this enzyme regulates the function of the channel, but also whether the channel regulates the enzyme, in particular, whether the association of the channel and enzyme render the enzyme responsive to changes in the voltage of the membrane, something usually only in the purview of specialized membrane proteins. Our specific aims are to: 1) characterize the protein motions underlying voltage sensing, 2) to understand how the closure of one gate influences the closure of another, and 3) to define the way that auxiliary ("beta") subunits in the reductase family modulate channels, and determine whether channels confer a voltage dependence onto reductase activity.
NIH ExPorter
NIH ExPorter