Structural Analysis of CavAb, a Prokaryotic Voltage-Gated Calcium Channel
Swanson, Teresa Mae
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Voltage-‐gated calcium channels are large membrane proteins that coordinate the movement of calcium into and out of the cell in response to changes in membrane potential, mediating signaling processes such as muscle contraction and synaptic transmission. We used CavAb, a bacterial calcium channel, as a structural model for three Cav channel characteristics; ion selectivity, drug binding, and disease mutations. First, CavAb reveals three binding sites for hydrated calcium within the selectivity filter of the channel, confirming the theory of a “knock-‐off” mechanism of calcium selectivity. Second, CavAb mimics mammalian Cav antagonist binding properties, providing visualization of bound drug molecules and potential direction for structure based drug design. Finally, the addition of Timothy Syndrome disease mutations into CavAb shows small conformational changes, highlighting the potential importance of channel regulation by lipids. Even though CavAb is a distant ancestor to the mammalian calcium channels, it has proven to be a valuable tool for answering classic calcium channel questions.
- Pharmacology