Exobiology and Evolutionary Biology

The Origin and Early Evolution of Ion Channels

PI: Andrew Pohorille

This proposal is devoted to investigations of the origin and early evolution of ion channels – protein assemblies that mediate ion transport across cell walls. This choice is motivated by the ubiquitous role of ion channels in the emergence of cellular life. Previously, we investigated how simple, protobiologically relevant proteins self-organize and self-assemble to form transmembrane channels that can efficiently mediate ion transport. In this proposal we focus on two other essential properties – selectivity towards specific types of ions and the ability to regulate fluxes of ions. In contemporary cells these two properties, especially regulation, require large, structurally and functionally complex protein segments. The ability to evolve selectivity and regulation placed ion channels at the center of fundamental cellular processes, such as energy and signal transduction in response to environmental signals.
Consistent with the general goals of this proposal, we have two specific aims. One is to examine how simple ion channels could become selective towards either cations or anions only through evolutionarily convenient local modifications, and how the channel size, shape and amino acid sequence influence selectivity. The other is to test a hypothesis that a simple, protobiologically relevant unit for regulating ion fluxes through ion channels might be a small assembly of water-soluble ?– helices attached to the transmembrane segments of channel-forming peptides. By modifying helix-helix interactions environmental signals could either promote or disrupt the assembly and, by doing so, either close or open the channel. To our knowledge, this is the first time that a hypothesis about the origin of regulation in membrane proteins has been put forward.

We will pursue our aims using computer modeling and simulations. We will examine model systems built of simple, natural or synthetic peptides that exhibit primitive selectivity and regulation. These systems will be selected for their significance, relevance to the origins of life, technical feasibility to model and the availability of experimental data needed for validating our simulations. We will further generalize our results in terms of their evolutionary implications for a broad range of similar systems.

The proposed studies directly address Goal 3 of the Astrobiology Roadmap, which deal with the origins of life on earth and elsewhere in the universe. By focusing on selective and regulated transport of ions across cell walls, which both facilitated and constrained evolution of protocells, this work is relevant to objectives 3.2 and 3.4 devoted to the origins and evolution of functional biomolecules and origins of cellularity and protobiological systems, respectively.