National Center for
3T9N: Crystal Structure Of A Membrane Protein
Structure and molecular mechanism of an anion-selective mechanosensitive channel of small conductance
Proc. Natl. Acad. Sci. U. S. A. (2012) 109 p.18180-18185
Mechanosensitive (MS) channels are universal cellular membrane pores. Bacterial MS channels, as typified by MS channel of small conductance (MscS) from Escherichia coli (EcMscS), release osmolytes under hypoosmotic conditions. MS channels are known to be ion selective to different extents, but the underlying mechanism remains poorly understood. Here we identify an anion-selective MscS channel from Thermoanaerobacter tengcongensis (TtMscS). The structure of TtMscS closely resembles that of EcMscS, but it lacks the large cytoplasmic equatorial portals found in EcMscS. In contrast, the cytoplasmic pore formed by the C-terminal beta-barrel of TtMscS is larger than that of EcMscS and has a strikingly different pattern of electrostatic surface potential. Swapping the beta-barrel region between TtMscS and EcMscS partially switches the ion selectivity. Our study defines the role of the beta-barrel in the ion selection of an anion-selective MscS channel and provides a structural basis for understanding the ion selectivity of MscS channels.