Unbiased search for structure/function correlates in K+ channels - Exploiting viral molecular evolution to study ion channel functionality

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The function of a K+-channel is mainly determined by its structure. The relevant complex and synergistic structure/function correlates, which operate in the folded protein, are commonly studied by comparing the function of structurally diverse orthologs. Here we propose a new approach, which should provide an unpreceeded high variability of K+-channel orthologs. The strategy is based on isolation and functional characterization of viral K+-channels from environmental samples, where Chlorella viruses are abundant. Nearly all these viruses contain a gene for a very small K+-channel under high selective pressure, as these channels are essential for host infection. In this project we will a) isolate viral DNA from diverse environmental samples, b) amplify contained viral K+-channel genes by specific viral K+-channel primers; c) build a rich sequence library of K+-channel orthologs; d) annotated these functionally by yeast complementation; e) determine in silico the (co)evolutionary signatures in the sequences and thus boundaries of evolutionary dynamics; f) build a library of necessary molecular dynamical details beyond simple structural insight, which are necessary for functional K+-channels; and g) gain insight into the evolutionary origins of viral proteins.