Functional characterization of gating polarity in CNBD channels across phylogenetically diverse species.

Abstract

The cyclic nucleotide binding domain (CNBD) family of the voltage-gated ion channel superfamily (VGIC) is involved in essential physiological processes, e.g. pacemaking, neuronal signaling, olfaction, and photoreception. CNBD channels are found in species throughout the tree of life, and for those with confirmed structures, show striking similarity in structure despite differences in gating polarity. Functional characterization from extant species closely related to ancestral species of each CNBD subfamily would provide more information regarding how functional divergence emerged while maintaining structural conservation. Here, we generated a phylogenetic tree of the CNBD family and functionally characterized the voltage sensitivity of extant species that are closest to each subclade's ancestral node. Our preliminary studies reveal that functional characterization of these extant species match with function of reported species that share the same subclade in our phylogenetic tree. Using this functional data, ancestral protein reconstruction of ancestral nodes of these subfamilies will be characterized and compared in upcoming future work to further elucidate what key residues drive the diversity in gating polarity in the CNBD channel family.