Abstract
In Escherichia coli (E. coli) the mechanosensitive channel of small conductance, MscS, gates in response to membrane tension created from acute external hypoosmotic shock, thus rescuing the bacterium from cell lysis. E. coli MscS is the most well studied member of the MscS superfamily of channels, whose members are found throughout the bacterial and plant kingdoms. Homology to the pore lining helix and upper vestibule domain of E. coli MscS is required for inclusion into the superfamily. Although highly conserved, in the second half of the pore lining helix (TM3B), E. coli MscS has five residues significantly different from other members of the superfamily. In superfamilies such as this, it remains unclear why variations within such a homologous region occur: is it tolerance of alternate residues, or does it define functional variance within the superfamily? Point mutations (S114I/T, L118F, A120S, L123F, F127E/K/T) and patch clamp electrophysiology were used to study the effect of changing these residues in E. coli MscS on sensitivity and gating. The data indicate that variation at these locations do not consistently lead to wildtype channel phenotypes, nor do they define large changes in mechanosensation, but often appear to effect changes in the E. coli MscS channel gating kinetics.
Highlights
Proteins are often classified into homology groups, or families, based on high sequence homology or similar functional roles
It remains unclear why variations within such a homologous region occur: is it tolerance of alternate residues, or does it define functional variance within the superfamily? In the mechanosensitive channel of small conductance (MscS) superfamily of channels, members are identified by homology to a highly conserved region of approximately 90 amino acids in the pore lining helix and the upper vestibule domain; outside of this region, the sequence
Members of the MscS superfamily of ion channels are identified by significant homology to an 87 amino acid region in Ec-MscS that starts at the pore lining helix and extends through the upper vestibule domain [1, 16, 17]
Summary
Proteins are often classified into homology groups, or families, based on high sequence homology or similar functional roles (functional homologues). For functional homologues, these family members often have diverse sequences but all complete the same function within the cell. In protein families where members are identified based on sequence homology to a particular region, the functional roles of these proteins has the potential to be quite diverse. It remains unclear why variations within such a homologous region occur: is it tolerance of alternate residues, or does it define functional variance within the superfamily? The 15 subfamilies of the MscS superfamily are unique due to additions on either the N-terminus or C-terminus to the family root channel Ec-MscS, such as additional transmembrane domains, ligand binding domains, large extracellular loops, and in some cases a domain that is predicted to interact with the outer membrane
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