CALCIUM-DEPENDENT REGULATION OF VOLTAGE-GATED CALCIUM CHANNELS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Voltage-gated calcium channels (CaVs) are multisubunit membrane proteins that allow the influx of extracellular calcium into the cytoplasm upon depolarization. They control secretion of neurotransmitters and hormones, initiation of muscle contraction, the pacemaker activity of heart cells, and gene transcription. Two calcium-dependent feedback processes regulate their activity: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Both processes are regulated by calmodulin (CaM) binding to the transmembrane subunit. In addition, several calcium binding proteins can reverse the effect of CaM. Here, we wish to perform diffraction experiments on crystals of complexes between different calcium binding proteins and their interaction domains from various types of CaVs. The resulting structures will provide valuable insight into how these complex proteins are regulated by calcium, and give a structural basis for the functional differences between the different CaV families.