Members of the Small Conductance Mechanosensitive Ion Channel (MscS) Family provide protection against hypo-osmotic shock in bacteria, responding both to stretching of the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

and to

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. ...

depolarization. In eukaryotes, they fulfill a multitude of important functions in addition to

osmoregulation Osmoregulation is the active regulation of the osmotic pressure of an organism's body fluids, detected by osmoreceptors, to maintain the homeostasis of the organism's water content; that is, it maintains the fluid balance and the concentration o ...

. They are present in the

s of organisms from the three domains of life: bacteria, archaea, fungi and plants.

Structure

There are two families of mechanosensitive (MS) channels: large-conductance MS channels (MscL) and small-conductance MS channels (MscS or YGGB). The MscS family is much larger and more variable in size and

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is calle ...

than the MscL family. MscS family homologues vary in length between 248 and 1120 amino acyl residues and in topology, but the homologous region that is shared by most of them is only 200-250 residues long, exhibiting 4-5

transmembrane A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...

regions (TMSs). Much of the diversity in MscS

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s occurs in the number of TMSs, which ranges from three to eleven TMSs, although the three C-terminal

helices A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is formed as two intertwined helices, ...

are conserved. Crystal structures of the ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'' MscS in the open and closed conformations are available. ''E. coli'' MscS folds as a homoheptamer with a cylindrical shape, and can be divided into transmembrane and extramembrane regions: an N-terminal

periplasm The periplasm is a concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the bacterial outer membrane called the ''periplasmic space'' in gram-negative bacteria. Using cryo-electron microscopy it has been found that ...

ic region, a

region, and a C-terminal

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

ic region (middle and C-terminal domains). The transmembrane region forms a channel through the

that opens into a chamber enclosed by the extramembrane portion, the latter connecting to the cytoplasm through distinct portals.

Function

MS channels function as electromechanical switches with the capability to sense the physical state of

lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...

s. Interactions with the membrane lipids are responsible for the sensing of mechanical force for most known MS channels. In bacterial and animal systems, MS ion channels are thought to mediate the perception of pressure, touch, and sound. 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. In addition, some MscS channels may function in

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

efflux, Ca²⁺ regulation and

cell division Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...

Transport reaction

The generalized transport reaction proposed for MscS channels is: :Osmolytes (in) and ions (in) ⇌ osmolytes (out) and ions (out)

Mechanism

Application of a ramp of negative pressure to a patch excised from an ''E. coli'' giant

spheroplast A spheroplast (or sphaeroplast in British usage) is a microbial cell from which the cell wall has been almost completely removed, as by the action of penicillin or lysozyme. According to some definitions, the term is used to describe Gram-negative ...

gave a small conductance (MscS; ~1 nS in 400 mM salt) with a sustained open state, and 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. Sensitivity towards tension changes can be explained as result of the hydrophobic coupling between the membrane and TMSs of the channel. Pockets in between TMSs were identified in MscS and YnaI that are filled with lipids. Fewer

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...

s 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.

References

{{CCBYSASource, sourcepath= http://www.tcdb.org/search/result.php?tc=1.a.23, sourcearticle= 1.A.23 The Small Conductance Mechanosensitive Ion Channel (MscS) Family , revision=699838558 Protein families Membrane proteins Transmembrane proteins Transmembrane transporters Transport proteins Integral membrane proteins Ion channels