Small MscS-like mechanosensitive channels: understanding minimal requirements for structure and function

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Mechanosensitive channels are the molecular basis of many important biological processes. One function is the stress response to hypoosmotic shock, which is essential for the survival of single-celled organisms in direct contact with the environment. One of these channels is the mechanosensitive channel of small conductance of Escherichia coli (EcMscS). It is the best characterized member of the largest and most diverse family of mechanosensitive channels. EcMscS is considered to be the mechanistic core because most of the other members of the family are larger with additional N-terminal or C-terminal extensions. Here, we want to investigate the rare examples of MscS-like channels that are smaller than EcMscS. We have chosen three examples from different domains of life: one channel comes from the Archaea Candidatus woesearchaeota archaeon (CwMscS), one from the bacterium, Francisella tularensis (FtMscS) and another from the protozoan Trypanosomas cruzi (TcMscS). These channels lack either N-terminal regions that contribute to the voltage sensing, or a characteristic vestibule that provides stability and selectivity, or both. We want to know what functional effects the structural minimization has. To answer this question, we will determine the molecular structures of the three smaller MscS-like channels with electron cryo microscopy and quantify the functional properties with electrophysiology. We expect to unveil essential nuts and bolts of an ancient, bio-molecular machine that is widely distributed across all domains of life.