1.A.23 The Small Conductance Mechanosensitive Ion Channel (MscS) Family

The MscS family (the SwissProt UPF0003 family) is a group of topographically diverse proteins, some of which are functionally characterized. They exhibit homology in only a restricted region. Early electrophysiological studies with E. coli suggested the presence of two distinguishable mechanosensitive ion channels, one with large conductance (MscL; TC #1.A.22) and one with small conductance (MscS; this family) (Martinac et al., 1987, 1990). Cytoplasmic beta domains appear to be new gating elements in MscS channels (Koprowski et al., 2011).  Open and closed conformational states of the heptameric channel have been proposed and discussed (Pliotas et al. 2012). Evolutionary considerations have been reported (Booth et al. 2015).  Some MscS channels may function in amino acid efflux, Ca2+ regulation and cell division (Cox et al. 2015).

Application of a ramp of negative pressure to a patch excised from an E. coli giant spheroplast gave (1) a small conductance (MscS; ~1 nS in 400 mM salt) with a sustained open state, and (2) a large conductance (MscL; ~3 nS) with faster kinetics, activated at higher pressure. MscS was reported to exhibit a weak anionic preference and a voltage dependency, tending to open upon depolarization. Activation by membrane-intercalating amphipathic compounds suggested that the MscS channel is sensitive to mechanical perturbations in the lipid bilayer. It was suggested that MscS plays a role in fast osmoregulatory responses. How these channels may respond to change in the mechanical environment the lipid bilayer provides is discussed by Kung et al. (2010).

Mechanosensitive channels function as electromechanical switches with the capability to sense the physical state of lipid bilayers. The X-ray crystal structures of MscL and MscS allow identification of the types of protein motions associated with the opening and closing of these structurally unrelated channels, while providing the framework to address a mechanism of tension sensing that is defined by channel-lipid interactions (Perozo and Rees, 2003). Functional, structural and dynamic data offer fresh insights into the molecular basis of gating for these membrane proteins.  Members of the MscS family are found in bacteria, archaea, fungi, and plants (Wilson et al. 2013).

Mutations in the genes encoding the KefA (AefA) and YggB proteins of E. coli block the MscS mechanosensitive channel activity. The principal one is affected by knockouts of YggB, while the minor one is affected by knockouts of KefA. These two channels open in response to pressure changes during osmotic downshift just below those that cause cell disruption and death (Biggin and Sansom, 2003; Pivetti et al., 2003). The C-termini of the YggB heptameric channel move apart upon channel opening and may serve as the gate (Koprowski and Kubalski, 2003). High resolution 3-D structures are available (Bass et al., 2002; Lai et al. 2013). Crosslinking studies indicate that a large conformational change accompanies the open to the closed configuration (Miller et al., 2003b).

Homologues of YggB are found in Gram-negative, Gram-positive and cyanobacteria, in archaea, in yeast and in plants, but not in animals (Booth and Louis, 1999). One archaeon, Haloferax volcanii, exhibits mechanosensitive channels similar in conductance and mass to YggB of E. coli, but the sequences of these channel proteins are not available (Le Dain et al., 1998). Two sequenced MscS homologues have been functionally characterized from Methanococcus jannaschii (Kloda and Martinac, 2001a,b).

MscS family homologues vary in length between 248 and 1120 amino acyl residues, but the homologous region that is shared by most of them is only 200-250 residues long, exhibiting 4-5 TMSs (Miller et al., 2003b). The topologies of these proteins differ drastically. YggB (286 aas; spP11666) exhibits 4-5 putative transmembrane α-helical spanners (TMSs); KefA (AefA) (1120 aas; spP77338) exhibits 11 TMSs; YjeP of E. coli (1107 aas; spP39285) exhibits 11 TMSs; YbiO of E. coli (741 aas; spP75783) exhibits 10 TMSs; and YbdG of E. coli (415 aas; spP39455) exhibits 5 TMSs. Moreover, of the M. jannaschii homologues, MJ0170 (350 aas; spQ57634) exhibits 4-5 TMSs; MJ0700 (324 aas; spQ58111) exhibits 4 TMSs; and MJ1143 (361 aas; spQ58543) exhibits 5-6 TMSs. This topological variability is an unusual characteristic of a family of homologous transport proteins, and its functional significance cannot be evaluated at this time. It is possible that transport mechanisms will vary in accordance with topology. On the other hand, only 2 TMSs, common to all of these proteins may comprise the channel (Booth and Louis, 1999).

The E. coli and Synechocystis genomes include five recognized paralogues of the MscS family while the Bacillus subtilis and Methanococcus jannaschii genomes include three paralogues. KefA is multidomain and may be multifunctional. It has a large (470 amino acyl residues) N-terminal extracytoplasmic domain that may interact with the peptidoglycan cell wall, a central hydrophobic region including the 11 TMSs (residues 480-940), and a C-terminal cytoplasmic domain (residues 941-1120). Only the last four TMSs and the C-terminal hydrophilic domain are homologous to the much shorter YggA protein. One of the Synechocystis homologues (slr1575) possesses a C-terminal domain homologous to cyclic AMP-dependent protein kinaseA regulatory subunits (Ochoa de Alde and Houmard, 2000). It may therefore be a cyclic nucleotide-regulated channel.

A homologue of MscS channels in Erwinia chrysanthemi, BspA, is encoded within an operon that includes the psd gene encoding phosphatidyl serine decarboxylase. In high salts medium, glycine betaine initially is taken up normally in a bspA mutant, but uptake is followed by reduced glucose uptake and release of glycine betaine without loss of viability. It was suggested that BspA is not a channel but instead senses the intracellular glycine betaine and the extracellular salt concentrations, and thus serves as a receptor for osmoadaptation (Touzé et al., 2001).

In bacterial and animal systems, mechanosensitive (MS) ion channels are thought to mediate the perception of pressure, touch, and sound. Ten MscS-Like (MSL) proteins are encoded within the genome of Arabidopsis thaliana. MSL2 and MSL3, along with MSC1, a MscS family member from green algae, are implicated in the control of organelle morphology. Haswell et al. (2008) characterized MSL9 and MSL10, two MSL proteins found in the plasma membrane of root cells. MSL9 and MSL10, along with three other members of the MSL family, are required for MS channel activities detected in protoplasts derived from root cells.

The Escherichia coli mechanosensitive channel, MscS, opens to allow rapid ion efflux, relieving the turgor pressure that would otherwise destroy the cell. Wang et al. (2008) described a 3.45 angstrom-resolution structure in an open conformation. MscS has a pore diameter of ~13 angstroms created by substantial rotational rearrangement of the three transmembrane helices. The structure suggests a molecular mechanism that underlies MscS gating and its decay of conductivity during prolonged activation (Wang et al., 2008). The levels of both MscL and MscS channels in Bacillus subtilis are high during exponential phase growth, very low in stationary phase and non-detectable in spores (Wahome et al., 2009). 

The E. coli MscS (EcMscS) has been extensively studied, but it may display characteristics not widely conserved in this protein family. With numerous members now electrophysiologically characterized, these channels displays a breadth of ion selectivity with both anion and cation selective members. The selectivities of these channels may be relatively weak in comparison to voltage-gated channels. Residues important for selectivity in MscS homologs suggest different selectivity mechanisms than those employed by voltage gated K+, Na+, Ca2+ and Cl- channels whose selectivity filters are housed within their transmembrane pores. Cox et al. 2013 attempted to unravel the potential physiological relevance of these differences. 

Mechanosensitive (MS) channels provide protection against hypo-osmotic shock in bacteria whereas eukaryotic MS channels fulfill a multitude of important functions in addition to osmoregulation. Interactions with the membrane lipids are responsible for the sensing of mechanical force for most known MS channels. Not only prokaryotic, but also eukaryotic, MS channels are able to directly sense the tension in the membrane bilayer without an additional cofactor. Sensitivity towards tension changes can be explained as result of the hydrophobic coupling between membrane and transmembrane (TM) regions of the channel. Molecular interactions of lipids with the channels may play an important role in mechanosensation. Pockets in between TM helices were identified in MscS and YnaI (TC# 1.A.23.4.3) that are filled with lipids. Fewer lipids are present in the open state of MscS than the closed. Thus, exclusion of lipid fatty acyl chains from these pockets, as a consequence of increased tension, may trigger gating. Similarly, in the eukaryotic MS channel TRAAK it was found that a lipid chain blocks the conducting path in the closed state (Rasmussen 2016).

The generalized transport reaction proposed for MscS channels is:

osmolytes (in) and ions (in) osmolytes (out) and ions (out).



This family belongs to the .

 

References:

Bass, R.B., P. Strop, M. Barclay, and D.C. Rees. (2002). Crystal structure of Escherichia coli MscS, a voltage-modulated and mechanosensitive channel. Science 298: 1582-1587.

Becker M. and Kramer R. (2015). MscCG from Corynebacterium glutamicum: functional significance of the C-terminal domain. Eur Biophys J. 44(7):577-88.

Becker, M., K. Börngen, T. Nomura, A.R. Battle, K. Marin, B. Martinac, and R. Krämer. (2013). Glutamate efflux mediated by Corynebacterium glutamicum MscCG, Escherichia coli MscS, and their derivatives. Biochim. Biophys. Acta. 1828: 1230-1240.

Bhagirath, A.Y., D. Somayajula, Y. Li, and K. Duan. (2017). CmpX Affects Virulence in Pseudomonas aeruginosa Through the Gac/Rsm Signaling Pathway and by Modulating c-di-GMP Levels. J. Membr. Biol. [Epub: Ahead of Print]

Biggin, P.C. and M.S. Sansom. (2003). Mechanosensitive channels: stress relief. Curr. Biol. 13: R183-185.

Booth, I.R. and P. Louis (1999). Managing hypoosmotic stress: aquaporins and mechanosensitive channels in Escherichia coli. Curr. Opin. Microbiol. 2: 166-169.

Booth, I.R., S. Miller, A. Müller, and L. Lehtovirta-Morley. (2015). The evolution of bacterial mechanosensitive channels. Cell Calcium 57: 140-150.

Bottcher B., Prazak V., Rasmussen A., Black SS. and Rasmussen T. (2015). The Structure of YnaI Implies Structural and Mechanistic Conservation in the MscS Family of Mechanosensitive Channels. Structure. 23(9):1705-14.

Caldwell, D.B., H.R. Malcolm, D.E. Elmore, and J.A. Maurer. (2010). Identification and experimental verification of a novel family of bacterial cyclic nucleotide-gated (bCNG) ion channels. Biochim. Biophys. Acta. 1798: 1750-1756.

Cox CD., Wann KT. and Martinac B. (201). Selectivity mechanisms in MscS-like channels: From structure to function. Channels (Austin). 8(1):5-12.

Cox, C.D., Y. Nakayama, T. Nomura, and B. Martinac. (2015). The evolutionary ''tinkering'' of MscS-like channels: generation of structural and functional diversity. Pflugers Arch 467: 3-13.

Edwards, M.D., S. Black, T. Rasmussen, A. Rasmussen, N.R. Stokes, T.L. Stephen, S. Miller, and I.R. Booth. (2012). Characterization of three novel mechanosensitive channel activities in Escherichia coli. Channels (Austin) 6: 272-281.

Hamilton, E.S., G.S. Jensen, G. Maksaev, A. Katims, A.M. Sherp, and E.S. Haswell. (2015). Mechanosensitive channel MSL8 regulates osmotic forces during pollen hydration and germination. Science 350: 438-441.

Haswell, E.S. and E.M. Meyerowitz. (2006). MscS-like proteins control plastid size and shape in Arabidopsis thaliana. Curr. Biol. 16: 1-11.

Haswell, E.S., R. Peyronnet, H. Barbier-Brygoo, E.M. Meyerowitz, and J.M. Frachisse. (2008). Two MscS homologs provide mechanosensitive channel activities in the Arabidopsis root. Curr. Biol. 18: 730-734.

Jensen, G.S. and E.S. Haswell. (2012). Functional analysis of conserved motifs in the mechanosensitive channel homolog MscS-Like2 from Arabidopsis thaliana. PLoS One 7: e40336.

Kloda, A. and B. Martinac. (2001a). Molecular identification of a mechanosensitive channel in archaea. Biophys. J. 80: 229–240.

Kloda, A. and B. Martinac. (2001b). Structural and functional differences between two homologous mechanosensitive channels of Methanococcus jannaschii. EMBO J. 20: 1888–1896.

Koprowski P., Sliwinska MA. and Kubalski A. (2015). Negative and positive temperature dependence of potassium leak in MscS mutants: Implications for understanding thermosensitive channels. Biochim Biophys Acta. 1848(8):1678-86.

Koprowski, P. and A. Kubalski. (2003). C termini of the Escherichia coli mechanosensitive ion channel (MscS) move apart upon the channel opening. J. Biol. Chem. 278: 11237-11245.

Koprowski, P., W. Grajkowski, E.Y. Isacoff, and A. Kubalski. (2011). Genetic screen for potassium leaky small mechanosensitive channels (MscS) in Escherichia coli: recognition of cytoplasmic β domain as a new gating element. J. Biol. Chem. 286: 877-888.

Kung, C., B. Martinac, and S. Sukharev. (2010). Mechanosensitive channels in microbes. Annu. Rev. Microbiol. 64: 313-329.

Lai JY., Poon YS., Kaiser JT. and Rees DC. (2013). Open and shut: crystal structures of the dodecylmaltoside solubilized mechanosensitive channel of small conductance from Escherichia coli and Helicobacter pylori at 4.4 A and 4.1 A resolutions. Protein Sci. 22(4):502-9.

Le Dain, A.C., N. Saint, A. Kloda, A. Ghazi and B. Martinac (1998). Mechanosensitive ion channels of the archeon Haloferax volcanii. J. Biol. Chem. 273: 12116-12119.

Levina, N., S. Tötemeyer, N.R. Stokes, P. Louis, M.A. Jones and I.R. Booth (1999). Protection of E. coli cells against extreme turgor by activation of MscS and MscL mechanosensitive channels: identification of genes required for MscS activity. EMBO J. 18: 1730-1737.

Maksaev, G., J.M. Shoots, S. Ohri, and E.S. Haswell. (2018). Nonpolar residues in the presumptive pore-lining helix of mechanosensitive channel MSL10 influence channel behavior and establish a nonconducting function. Plant Direct 2:.

Malcolm, H.R., P. Blount, and J.A. Maurer. (2015). The mechanosensitive channel of small conductance (MscS) functions as a Jack-in-the box. Biochim. Biophys. Acta. 1848: 159-166.

Malcolm, H.R., Y.Y. Heo, D.E. Elmore, and J.A. Maurer. (2011). Defining the role of the tension sensor in the mechanosensitive channel of small conductance. Biophys. J. 101: 345-352.

Martinac, B., J. Adler and C. Kung (1990). Mechanosensitive channels of E. coli activated by amphipaths. Nature 348: 261-263.

Martinac, B., M. Buechner, A.H. Delcour, J. Adler and C. Kung (1987). Pressure-sensitive ion channel in Escherichia coli. Proc. Natl. Acad. Sci. USA 84: 2297-2301.

Miller, S., M.D. Edwards, C. Ozdemir, and I.R. Booth. (2003b). The closed structure of the MscS mechanosensitive channel. Cross-linking of single cysteine mutants. J. Biol. Chem. 278: 32246-32250.

Miller, S., W. Bartlett, S. Chandrasekaran, S. Simpson, M. Edwards, and I.R. Booth. (2003a). Domain organization of the MscS mechanosensitive channel of Escherichia coli. EMBO J. 22: 36-46.

Moraes, T.F. and R.A. Reithmeier. (2012). Membrane transport metabolons. Biochim. Biophys. Acta. 1818: 2687-2706.

Nakayama, Y., K. Fujiu, M. Sokabe, and K. Yoshimura. (2007). Molecular and electrophysiological characterization of a mechanosensitive channel expressed in the chloroplasts of Chlamydomonas. Proc. Natl. Acad. Sci. USA 104: 5883-5888.

Nomura, T., M. Sokabe, and K. Yoshimura. (2016). Voltage-Dependent Inactivation of MscS Occurs Independently of the Positively Charged Residues in the Transmembrane Domain. Biomed Res Int 2016: 2401657.

Ochoa de Alda, J. and J. Houmard (2000). Genomic survey of cAMP and cGMP signalling components in the cyanobacterium Synechocystis PCC 6803. Microbiology 146: 3183-3194.

Perozo, E. and D.C. Rees. (2003). Structure and mechanism in prokaryotic mechanosensitive channels. Curr. Opin. Struct. Biol. 13: 432-442.

Pivetti, C.D., M.-R. Yen, S. Miller, W. Busch, Y.-H. Tseng, I.R. Booth, and M.H. Saier, Jr. (2003). Two families of mechanosensitive channel proteins. Microbiol. Mol. Biol. Rev. 67: 66-85.

Pliotas, C., R. Ward, E. Branigan, A. Rasmussen, G. Hagelueken, H. Huang, S.S. Black, I.R. Booth, O. Schiemann, and J.H. Naismith. (2012). Conformational state of the MscS mechanosensitive channel in solution revealed by pulsed electron-electron double resonance (PELDOR) spectroscopy. Proc. Natl. Acad. Sci. USA 109: E2675-2682.

Rasmussen T., Rasmussen A., Singh S., Galbiati H., Edwards MD., Miller S. and Booth IR. (2015). Properties of the Mechanosensitive Channel MscS Pore Revealed by Tryptophan Scanning Mutagenesis. Biochemistry. 54(29):4519-30.

Rasmussen, T. (2016). How do mechanosensitive channels sense membrane tension? Biochem Soc Trans 44: 1019-1025.

Rowe, I., A. Anishkin, K. Kamaraju, K. Yoshimura, and S. Sukharev. (2014). The cytoplasmic cage domain of the mechanosensitive channel MscS is a sensor of macromolecular crowding. J Gen Physiol 143: 543-557.

Schumann, U., M.D. Edwards, T. Rasmussen, W. Bartlett, P. van West, and I.R. Booth. (2010). YbdG in Escherichia coli is a threshold-setting mechanosensitive channel with MscM activity. Proc. Natl. Acad. Sci. USA 107: 12664-12669.

Sukharev, S.I., P. Blount, B. Martinac, H.R. Guy and C. King (1996). MscL: a mechanosensitive channel in Escherichia coli. In: Organellar Ion Channels and Transporters (D. E. Clapham and B. E. Ehrlich, eds.). Rockefeller University Press, New York, pp. 133-141.

Touzé, T., G. Gouesbet, C. Boiangiu, M. Jebbar, S. Bonnassie, and C. Blanco. (2001). Glycine betaine loses its osmoprotective activity in a bspAstrain of Erwinia chrysanthemi. Mol. Microbiol. 42: 87-99.

Wahome, P.G., A.E. Cowan, B. Setlow, and P. Setlow. (2009). Levels and localization of mechanosensitive channel proteins in Bacillus subtilis. Arch. Microbiol. 191: 403-414.

Wang, W., S. Black, M.D. Edwards, S. Miller, E.L. Morrision, W. Bartlett, C. Dong, J.H. Naismith, and I.R. Booth. (2008).  The structure of an open form of an E. coli mechanosensitive channel at 3.45 A Resoluton.  Science 321: 1179-1214. 

Wang, Y., G. Cao, D. Xu, L. Fan, X. Wu, X. Ni, S. Zhao, P. Zheng, J. Sun, and Y. Ma. (2018). A Novel l-Glutamate Exporter of. Appl. Environ. Microbiol. [Epub: Ahead of Print]

Wilson, M.E., G. Maksaev, and E.S. Haswell. (2013). MscS-like mechanosensitive channels in plants and microbes. Biochemistry 52: 5708-5722.

Wilson, M.E., M.R. Basu, G.B. Bhaskara, P.E. Verslues, and E.S. Haswell. (2014). Plastid osmotic stress activates cellular stress responses in Arabidopsis. Plant Physiol. 165: 119-128.

Yu, J., B. Zhang, Y. Zhang, C.Q. Xu, W. Zhuo, J. Ge, J. Li, N. Gao, Y. Li, and M. Yang. (2017). A binding-block ion selective mechanism revealed by a Na/K selective channel. Protein Cell. [Epub: Ahead of Print]

Zhu, L., Q. Cui, H. Xiao, X. Liao, and X. Chen. (2018). Gating and inactivation of mechanosensitive channels of small conductance: A continuum mechanics study. J Mech Behav Biomed Mater 90: 502-514. [Epub: Ahead of Print]

Examples:

TC#NameOrganismal TypeExample
1.A.23.1.1

Minor K+-dependent MscS-type mechanosensitive channel protein, designated KefA, AefA or MscK, (Edwards et al. 2012).

Bacteria, archaea, yeast, plants

KefA (AefA) of E. coli

 
1.A.23.1.2The putative osmoadaptation receptor, BspABacteriaBspA of Erwinia (Pectobacterium) chrysanthemi
 
1.A.23.1.3

Mini conductance (300 pS) mechanosensitive channel, YjeP or MscM (1107aas; 13 TMSs in a 1 + 12 TMS arrangement).  Encoded in an operon with phosphatidyl serine decarboxylase (Moraes and Reithmeier 2012). Protects against hypoosmotic shock (Edwards et al. 2012).

Bacteria

YjeP of E. coli (P39285)

 
1.A.23.1.4

Uncharacterized protein of 571 aas and 6 TMSs.

UP of Bdellovibrio exovorus

 
Examples:

TC#NameOrganismal TypeExample
1.A.23.2.1

Major MscS channel protein, YggB. Seven residues, mostly hydrophobic, in the first and second transmembrane helices are lipid-sensing residues (Malcolm et al., 2011).  X-ray structures are available (Lai et al. 2013).  The cytoplasmic cage domain senses macromolecular crowding (Rowe et al. 2014). A gating mechanism has been proposed (Malcolm et al. 2015).  The thermodynamics of K+ leak have been studied (Koprowski et al. 2015).  In the MscS crystal structure (PDB 2OAU ), a narrow, hydrophobic opening is visible in the crystal structure, and a vapor lock, created by hydrophobic seals consisting of L105 and L109, is the barrier to water and ions (Rasmussen et al. 2015). The voltage dependence of inactivation occurs independently of the positive charges of R46, R54, and R74 (Nomura et al. 2016).

Protobacteria; homologues are found in archaea, yeast and plants.

YggB of E. coli (P0C0S1)

 
1.A.23.2.2

MscS protein.  The x-ray structure at 4.2 Å is available (Lai et al. 2013).

Proteobacteria

MscS of Helicobacter pylori

 
1.A.23.2.3

MscS mechanosensitive channel of 462 aas and 5 TMSs.

MscS channel of Candidatus Peribacter riflensis

 
1.A.23.2.4

Putative small conductance mechanosensetive channel protein of 261 aas and 3 TMSs

MscS homologue of Aureococcus anophagefferens virus

 
Examples:

TC#NameOrganismal TypeExample
1.A.23.3.1The YkuT osmolyte efflux channel Bacteria, archaea, yeast, plants YkuT of Bacillus subtilis
 
1.A.23.3.2

Mechanosensitive NaCl-inducible RpoS-dependent channel (1,000 pS), YbiO (741 aas; 10TMSs).  Protects agains hypoosmotic shock (Edwards et al. 2012).

Bacteria

YbiO of E. coli (P75783)

 
1.A.23.3.3

Mechanosensitive channel, small conductance, YggB or MscCG (533 aas; 6-7 TMSs).  Mediates glutamate efflux (Becker et al. 2013).  The pore domain is in the N-terminus.  The C-terminus includes three subdomains, the periplasmic loop, the fourth transmembrane segment, and the cytoplasmic loop, all of which are important for MscCG function, in particular for glutamate excretion (Becker and Krämer 2015).

 

Actinobacteria

YggB or MscCG of Corynebacterium glutamicum (P42531)

 
1.A.23.3.4

MscCG2 of 334 aas and 4 TMSs in a 3 + 1 arrangement.  It functions as an L-glutamate exporter and an osmotic safety valve (Wang et al. 2018). It is 23% identical to MscCG (TC# 1.A.23.3.3) in the same organism. MscCG2-mediated L-glutamate excretion was activated by biotin limitation or penicillin treatment, and constitutive L-glutamate excretion was triggered by a gain-of-function mutation (A151V). It was not induced by glutamate producing conditions (Wang et al. 2018).

MscCG2 of Corynebacterium glutamicum

 
Examples:

TC#NameOrganismal TypeExample
1.A.23.4.1The MscMJ mechanosensitive channelBacteria, archaea, yeast, plantsMscMJ of Methanococcus jannaschii
 
1.A.23.4.10

Uncharacterized MscS homologue

Proteobacteria

MscS homologue of Helicobacter pylori

 
1.A.23.4.11

MscS-like channel, MSL1. Mechanosensitive ion channel protein 1, mitochondrial.

Plants

MSL1 of Arabidopsis thaliana

 
1.A.23.4.12

Uncharacterized MscS channel of 351 aas and 4 N-terminal TMSs.

UP of Bdellovibrio bacteriovorus

 
1.A.23.4.13

MscS channel of 553 aas and 6 TMSs.

MscS of Entamoeba histolytica

 
1.A.23.4.14

Mechanosensitive channel-like 10, Msl10 of 734 aas and 5 or more TMSs.  Functions in triggering cell death in a process that is independent of its channel activity (Maksaev et al. 2018).

Mscl10 of Arabidopsis thaliana (Mouse-ear cress)

 
1.A.23.4.2The MscMJLR mechanosensitive channelBacteria, archaea, yeast, plantsMscMJLR of Methanococcus jannaschii
 
1.A.23.4.3

Mechanosensative cation-selective channel with a conductance of 100 pS, YnaI (344aas; 4TMSs).  Protects against hypoosmotic shock (Edwards et al. 2012).  The structure has been solved by cryo-electron microscopy to a resolution of 13 A (Böttcher et al. 2015). While the cytosolic vestibule is structurally similar to that in MscS, additional density is seen in the transmembrane region, consistent with the presence of two additional TMSs predicted for YnaI. The location of this density suggests that the extra TMSs are tilted, which could induce local membrane curvature extending the tension-sensing paddles seen in MscS. Off-center lipid-accessible cavities are seen that resemble gaps between the sensor paddles in MscS. The conservation of the tapered shape and the cavities in YnaI suggest a mechanism similar to that of MscS (Böttcher et al. 2015). The voltage dependence of inactivation occurs independently of the positive charges of R46, R54, and R74 (Nomura et al. 2016). A 3.8 Å structure by cryoEM revealed a heptamer structural fold similar to previously studied MscS channels. The ion-selective filter is formed by seven hydrophobic methionines (Met158) in the transmembrane pore (Yu et al. 2017). Details of the gating transition for MscS have been predicted (Zhu et al. 2018).

Proteobacteria

YnaI of E. coli (P0AEB5)

 
1.A.23.4.4

Plant plastid mechanosensitive channel MscS-like-2 (Msl2) (controls plastid organellar morphology, as does Msl3) (Haswell and Meyerowitz, 2006Haswell et al., 2008). It functions as do the bacterial homologues, but is essential for leaf growth, chloroplast integrity and normal starch accumulation (Jensen and Haswell 2012).  msl2 msl3 double mutant seedlings exhibit several hallmarks of drought or environmental osmotic stress, including solute accumulation, elevated levels of the compatible osmolyte proline (Pro), and accumulation of the stress hormone abscisic acid (ABA). Furthermore, msl2 msl3 mutants expressed Pro and ABA metabolism genes in a pattern normally seen under drought or osmotic stress. Pro accumulation in the msl2 msl3 mutant was suppressed by conditions that reduce plastid osmotic stress leading to the conclusion that these channels function like their bacterial homologues (Wilson et al. 2014).

Plant

Msl2 of Arabidopsis thaliana (Q56X46)

 
1.A.23.4.5

MscM (YbdG) is a distant member of the MscS family. It displays miniconductance (MscM) activity (Schumann et al., 2010; Edwards et al. 2012).

Bacteria

MscM (YbdG) of E. coli (P0AAT4)

 
1.A.23.4.6

Mechanosensitive channel, MscS

Archaea

MscS of Sulfolobus islandicus (C4KE93)

 
1.A.23.4.7

Mechanosensitive ion channel protein 8 (Mechanosensitive channel of small conductance-like 8) (MscS-Like protein 8) is a pollen-specific, membrane tension-gated ion channel required for pollen to survive the hypoosmotic shock of rehydration and for full male fertility. It negatively regulates pollen germination but is required for cellular integrity during germination and tube growth. MSL8 thus senses and responds to changes in membrane tension associated with pollen hydration and germination (Hamilton et al. 2015).

Plants

MSL8 of Arabidopsis thaliana

 
1.A.23.4.8Mechanosensitive ion channel protein 5 (Mechanosensitive channel of small conductance-like 5) (MscS-Like protein 5)PlantsMSL5 of Arabidopsis thaliana
 
1.A.23.4.9

Putative small conductance mechanosensitive channel; Calcium channel, MacS

Fungi

MacS of Mycosphaerella graminicola (Zymoseptoria tritici)

 
Examples:

TC#NameOrganismal TypeExample
1.A.23.5.1

The cyclic nucleotide-binding MscS homologue, MT2508 (the C-terminal domain is the CAP_ED domain CD00038). It lacks mechanosensitivity but is ligand-gated by cyclic nucleotides (Caldwell et al., 2010).

Bacteria

MscS homologue, MT2508 of Mycobacterium tuberculosis (P71915)

 
Examples:

TC#NameOrganismal TypeExample
1.A.23.6.1Chloroplast mechanosensitive channel, Msc1 (anions are preferred over cations) (Nakayama et al., 2007).

Algae

Msc1 of Chlamydomonas reinhardtii (A3KE12)

 
Examples:

TC#NameOrganismal TypeExample
1.A.23.7.1

MscS homologue

Actinobacteria

MscS homologue of Streptomyces coelicolor

 
1.A.23.7.2

MscS homologue

Proteobacteria

MscS of Myxococcus xanthus

 
Examples:

TC#NameOrganismal TypeExample
1.A.23.8.1

CmpX of 274 aas and 5 TMSs in a 1 + 4 arrangement. CmpX regulates virulence and controls biofilm formation in P. aeruginosa (Bhagirath et al. 2017). It also modulates intra-cellular c-di-GMP levels. A cmpX knockout showed decreased promoter activity of exoS (PA1362) and increased activity of the small RNA, RsmY. As compared to the wild-type PAO1, the cmpX mutant had elevated intracellular c-di-GMP levels as well as increased expression of wspR (PA3702), a c-di-GMP synthase. Transcription of the major outer membrane porin gene oprF (PA1777) and sigma factor sigX (PA1776) was decreased in the cmpX mutant. The cmpX knockout mutant had increased sensitivity to membrane detergents and antibiotics such as lauryl sulfobetaine, tobramycin, and vancomycin (Bhagirath et al. 2017).

CmpX of Pseudomonas aeruginosa

 
1.A.23.8.2

CmpX protein of 227 aas and 5 TMSs

CmpX of Candidatus Wolfebacteria bacterium

 
1.A.23.8.3

Uncharacterized protein of 439 aas and 9 TMSs in a 5 + 4 arrangement.

UP of Brevundimonas viscosa

 
1.A.23.8.4

Mechanosensitive ion channel protein MscS of 254 aas and 5 TM

MscS of Haloterrigena daqingensis

 
1.A.23.8.5

Uncharacterized protein of 486 aas and 11 TMSs.

UP of Hydrogenophaga taeniospiralis