New lab publications

We had a couple of nice publications late last year that are worth a mention:

The S6 gate in regulatory Kv6 subunits restricts heteromeric K+ channel stoichiometry

This paper was the core of Aditya’s thesis and is a great example of how you can use evolution to highlight key features of proteins. K+ channels are tetrameric and can typically form as homotetramers composed of four identical subunits. However, some subunits have evolved a “regulatory” phenotype in which they can no longer make homotetramers and instead depend on mixing with other closely-related K+ channel subunits to form functional channels, often in an unusual asymmetric 3:1 ratio. We identified sequence changes that correlated with evolution of the regulatory phenotype and found that the interface between subunits in the lining of the pore itself played a key role in determining channel composition. Previously, it had been thought that a cytoplasmic sorting domain, T1, was fully responsible for channel subunit composition. We proposed a two-step model of how you can evolve asymmetric channels that involves sequential mutation of T1 and the pore. This is one of those typical JGP papers with heroically complicated biophysics experiments. We also received a great assist from the Hancock lab who worked with us to count subunits in individual channels using fluorescent tags.

Evolution and Structural Characteristics of Plant Voltage-Gated K+ Channels

This a review Greg and I wrote with Sally on the evolution of Plant Voltage-Gated K+ channels and the CNBD channel superfamily to which they belong. We managed to squeeze a lot of new analyses into it, so its sort of a hybrid review/research article. Here is my favorite thing in the article: 1) CNBD superfamily channels, which include the plant channels and a wide range of animal channels that control sensory perception, neuronal excitability and heartbeat, come from a prokaryotic ancestor that is common in eubacterial lineages but appears to be absent (at least so far) in the Archaea. Since eukaryotes evolved from the Archaeal lineage, that could mean we picked up the CNBD channel superfamily by lateral gene transfer. There of course are plenty of documented cases of lateral gene transfer, but I still think its amazing that the channels that we use to see and smell and the channels that plants depend on to open and close their leaf pores may have been “borrowed” from bacteria. The Plant Cell is of course nothing new to Sally, but it was nice for me to bag another top journal for my “life list”.