# Modular architecture of K+ channels: the functional plasticity of the pore module

## TL;DR

The paper explores how potassium channel pores evolved and can be used to design synthetic channels with new functions.

## Contribution

It shows that the pore module of K+ channels has inherent functional plasticity that can be harnessed for synthetic biology.

## Key findings

- Kcv channels can generate gating phenomena typical of complex mammalian channels through mutations.
- The modular design of K+ channels allows synthetic channels with novel sensitivities like light or Ca2+.
- Evolutionary trends in K+ channels can be mimicked by coupling pore units with sensor domains.

## Abstract

Miniature K+ channel proteins from viruses (Kcv) are structurally and functionally equivalent to the pore module of all K+ channels. Here, we summarize data in support of the hypothesis that pores of primitive K+ channels served as building blocks for evolving the modern complex mammalian ion channels. Experimental data show that mutations in Kcv channels can generate gating phenomena like slow-activating inward or outward rectification, which are typical of complex mammalian channels. Hence, the basic mechanism for rectification is an inherent property of the pore module, which was further tuned and/or amplified during evolution by the addition of sensory protein domains. This evolutionary trend can be experimentally mimicked by coupling small pore units with a voltage-sensing domain or a glutamate-binding domain to acquire voltage and ligand-sensitive gating. The same modularity principle can be exploited in the design of synthetic channels in which the Kcv pore is coupled to orthogonal sensor domains. These synthetic channels exhibit new gating properties like a sensitivity to light or Ca2+, which originate from their attached sensor domains.

This review discusses the modular building principles of K+ channels in the context of evolution of complex ion channels and the design of synthetic channels.