|Gene:||mscS||Accession Numbers: EG11160 (EcoCyc), b2924, ECK2920|
MscS is a mechanosensitive channel of small conductance; MscS conductance is 0.8-1 nanosiemens in E. coli giant protoplasts [Levina99].
MscS activity is adaptive, that is, it declines in response to sustained stimulation [Koprowski98]. In patch clamp experiments MscS activity occurs in short bursts that last for a few seconds [Levina99]. Gating of MscS is controlled by tension within, or voltage across the lipid bilayer [Sukharev93, Sukharev02]. Activation of MscS depends upon tension, while inactivation is both tension and voltage dependent; channel activation requires a high rate of increase in membrane tension; slower rates of increase can be ignored [Akitake05].
MscS is a homoheptamer [Bass02, Stenberg05]; with three transmembrane (TM) domains per subunit and a large cytoplasmic chamber [Bass02]. The N-terminus of each subunit forms a mixed helical hairpin structure located at the periplasmic interface of the lipid bilayer [Vasquez08]. The functional state represented in the crystal structure of [Bass02] - conducting [Spronk06] or non-conducting [Anishkin04, Sotomayor06, Sotomayor07] - is unclear. A model for closed [Vasquez08] and open [Anishkin08, Vasquez08a] conformations of MscS have been proposed.
The inhibition of MscS channel activity due to crosslinking of the C-terminus or adding Ni2+ to C-terminally, hexahistidine tagged proteins suggests that the C-terminus acts as a cytoplasmic gate and moves apart upon activation of the channel [Koprowski03]. Deletion of the C-terminus of MscS resulted in decreased stability and activity [Schumann04]. Crosslinking studies of cysteine substitutions reveal the very flexible architecture of the MscS channel and support the crystal structure and the prediction that MscS undergoes dramatic displacement of domains upon activation and deactivation [Miller03]. The structural rearrangements associated with MscS activation in membranes have been studied using functorial measurements, electron paramagnetic resonance (EPR) spectroscopy, and computational analyses [Vasquez08a].
Parabens induce MscS activity which allows leakage of cell contents, suggesting a mechanism for their antimicrobial activity [Nguyen05] although later experiments [Kamaraju08] suggest that MscS may not be the primary target for parabens. MscS is slightly anion-selective [Sukharev93].
The potassium dependent mechanosensitive channel MscK, contributes to small conductance channel activity in E. coli protoplasts but KefA channel activity does not desensitize on extended application of pressure; deletion of mscS eliminates the majority of small conductance channel activity [Levina99].
mscS expression is induced by RpoS upon entry into stationary phase and by osmotic stress [Stokes03].
Seven mechanosensitive ion channels have been characterised in E. coli K-12: MscL, MscS, MscK, MscM, YnaI, YbiO and YbdG. A strain lacking all seven of these proteins fails to demonstrate channel opening in patch clamp experiments [Edwards12].
mscS: mechanosensitive channel of small conductance
Locations: inner membrane
|Map Position: [3,066,969 <- 3,067,829] (66.1 centisomes, 238°)||Length: 861 bp / 286 aa|
Molecular Weight of Polypeptide: 30.896 kD (from nucleotide sequence), 31.0 kD (experimental) [Sukharev02 ]
Unification Links: ASAP:ABE-0009595 , DIP:DIP-36192N , EchoBASE:EB1149 , EcoGene:EG11160 , EcoliWiki:b2924 , ModBase:P0C0S1 , OU-Microarray:b2924 , PortEco:mscS , PR:PRO_000023297 , Pride:P0C0S1 , Protein Model Portal:P0C0S1 , RefSeq:NP_417399 , RegulonDB:EG11160 , SMR:P0C0S1 , String:511145.b2924 , Swiss-Model:P0C0S1 , UniProt:P0C0S1
Relationship Links: InterPro:IN-FAMILY:IPR006685 , InterPro:IN-FAMILY:IPR006686 , InterPro:IN-FAMILY:IPR008910 , InterPro:IN-FAMILY:IPR010920 , InterPro:IN-FAMILY:IPR011014 , InterPro:IN-FAMILY:IPR011066 , PDB:Structure:2OAU , PDB:Structure:2VV5 , PDB:Structure:3UDC , PDB:Structure:4AGE , PDB:Structure:4AGF , PDB:Structure:4HWA , Pfam:IN-FAMILY:PF00924 , Pfam:IN-FAMILY:PF05552 , Prosite:IN-FAMILY:PS01246
In Paralogous Gene Group: 133 (3 members)
|Biological Process:||GO:0009992 - cellular water homeostasis
GO:0034220 - ion transmembrane transport [Sukharev02]
GO:0006810 - transport [UniProtGOA11a]
GO:0006811 - ion transport [UniProtGOA11a]
GO:0055085 - transmembrane transport [GOA01a]
|Molecular Function:||GO:0008381 - mechanically-gated ion channel activity [Sukharev02]|
|Cellular Component:||GO:0016021 - integral component of membrane
[UniProtGOA11a, Sukharev02, Berrier89]
GO:0005886 - plasma membrane [UniProtGOA11, UniProtGOA11a, Berrier89]
GO:0016020 - membrane [UniProtGOA11a, GOA01a]
|MultiFun Terms:||cell processes → adaptations → other (mechanical, nutritional, oxidative stress)|
|cell structure → membrane|
|transport → Channel-type Transporters → alpha-type channels|
|Growth Medium||Growth?||T (°C)||O2||pH||Osm/L||Growth Observations|
|LB Lennox||Yes||37||Aerobic||7||Yes [Baba06, Comment 1]|
|M9 medium with 1% glycerol||Yes||37||Aerobic||7.2||0.35||Yes [Joyce06, Comment 2]|
|MOPS medium with 0.4% glucose||Yes||37||Aerobic||7.2||0.22||Yes [Baba06, Comment 1]|
Enzymatic reaction of: mechanosensitive channel MscS
|Feature Class||Location||Common Name||Citations||Comment|
|Transmembrane-Region||29 -> 57||TM1|
|Transmembrane-Region||68 -> 91||TM2|
|Transmembrane-Region||96 -> 113|
|Transmembrane-Region||96 -> 127||TM3|
|Mutagenesis-Variant||266 -> 286|
10/20/97 Gene b2924 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11160; confirmed by SwissProt match.
Akitake07: Akitake B, Spelbrink RE, Anishkin A, Killian JA, de Kruijff B, Sukharev S (2007). "2,2,2-Trifluoroethanol changes the transition kinetics and subunit interactions in the small bacterial mechanosensitive channel MscS." Biophys J 92(8);2771-84. PMID: 17277184
Anishkin08: Anishkin A, Kamaraju K, Sukharev S (2008). "Mechanosensitive channel MscS in the open state: modeling of the transition, explicit simulations, and experimental measurements of conductance." J Gen Physiol 132(1);67-83. PMID: 18591417
Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554
Bass03: Bass RB, Locher KP, Borths E, Poon Y, Strop P, Lee A, Rees DC (2003). "The structures of BtuCD and MscS and their implications for transporter and channel function." FEBS Lett 555(1);111-5. PMID: 14630329
Berrier89: Berrier C, Coulombe A, Houssin C, Ghazi A (1989). "A patch-clamp study of ion channels of inner and outer membranes and of contact zones of E. coli, fused into giant liposomes. Pressure-activated channels are localized in the inner membrane." FEBS Lett 259(1);27-32. PMID: 2480919
Chiang04: Chiang CS, Anishkin A, Sukharev S (2004). "Gating of the large mechanosensitive channel in situ: estimation of the spatial scale of the transition from channel population responses." Biophys J 86(5);2846-61. PMID: 15111402
Edwards05: Edwards MD, Li Y, Kim S, Miller S, Bartlett W, Black S, Dennison S, Iscla I, Blount P, Bowie JU, Booth IR (2005). "Pivotal role of the glycine-rich TM3 helix in gating the MscS mechanosensitive channel." Nat Struct Mol Biol 12(2);113-9. PMID: 15665866
Edwards12: Edwards MD, Black S, Rasmussen T, Rasmussen A, Stokes NR, Stephen TL, Miller S, Booth IR (2012). "Characterization of three novel mechanosensitive channel activities in Escherichia coli." Channels (Austin) 6(4);272-81. PMID: 22874652
Grajkowski05: Grajkowski W, Kubalski A, Koprowski P (2005). "Surface changes of the mechanosensitive channel MscS upon its activation, inactivation, and closing." Biophys J 88(4);3050-9. PMID: 15665126
Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394
Kamaraju08: Kamaraju K, Sukharev S (2008). "The membrane lateral pressure-perturbing capacity of parabens and their effects on the mechanosensitive channel directly correlate with hydrophobicity." Biochemistry 47(40);10540-50. PMID: 18795793
Levina99: Levina N, Totemeyer S, Stokes NR, Louis P, Jones MA, Booth IR (1999). "Protection of Escherichia coli cells against extreme turgor by activation of MscS and MscL mechanosensitive channels: identification of genes required for MscS activity." EMBO J 1999;18(7);1730-7. PMID: 10202137
Miller03: Miller S, Edwards MD, Ozdemir C, Booth IR (2003). "The closed structure of the MscS mechanosensitive channel. Cross-linking of single cysteine mutants." J Biol Chem 278(34);32246-50. PMID: 12767977
Miller03a: Miller S, Bartlett W, Chandrasekaran S, Simpson S, Edwards M, Booth IR (2003). "Domain organization of the MscS mechanosensitive channel of Escherichia coli." EMBO J 22(1);36-46. PMID: 12505982
Okada02: Okada K, Moe PC, Blount P (2002). "Functional design of bacterial mechanosensitive channels. Comparisons and contrasts illuminated by random mutagenesis." J Biol Chem 277(31);27682-8. PMID: 12015316
Pivetti03: Pivetti CD, Yen MR, Miller S, Busch W, Tseng YH, Booth IR, Saier MH (2003). "Two families of mechanosensitive channel proteins." Microbiol Mol Biol Rev 67(1);66-85, table of contents. PMID: 12626684
Schumann04: Schumann U, Edwards MD, Li C, Booth IR (2004). "The conserved carboxy-terminus of the MscS mechanosensitive channel is not essential but increases stability and activity." FEBS Lett 572(1-3);233-7. PMID: 15304354
Sotomayor06: Sotomayor M, van der Straaten TA, Ravaioli U, Schulten K (2006). "Electrostatic properties of the mechanosensitive channel of small conductance MscS." Biophys J 90(10);3496-510. PMID: 16513774
Spronk06: Spronk SA, Elmore DE, Dougherty DA (2006). "Voltage-dependent hydration and conduction properties of the hydrophobic pore of the mechanosensitive channel of small conductance." Biophys J 90(10);3555-69. PMID: 16500980
Stenberg05: Stenberg F, Chovanec P, Maslen SL, Robinson CV, Ilag LL, von Heijne G, Daley DO (2005). "Protein complexes of the Escherichia coli cell envelope." J Biol Chem 280(41);34409-19. PMID: 16079137
Stokes03: Stokes NR, Murray HD, Subramaniam C, Gourse RL, Louis P, Bartlett W, Miller S, Booth IR (2003). "A role for mechanosensitive channels in survival of stationary phase: regulation of channel expression by RpoS." Proc Natl Acad Sci U S A 100(26);15959-64. PMID: 14671322
Sukharev02: Sukharev S (2002). "Purification of the small mechanosensitive channel of Escherichia coli (MscS): the subunit structure, conduction, and gating characteristics in liposomes." Biophys J 83(1);290-8. PMID: 12080120
Sukharev93: Sukharev SI, Martinac B, Arshavsky VY, Kung C (1993). "Two types of mechanosensitive channels in the Escherichia coli cell envelope: solubilization and functional reconstitution." Biophys J 65(1);177-83. PMID: 7690260
Vasquez08: Vasquez V, Sotomayor M, Cortes DM, Roux B, Schulten K, Perozo E (2008). "Three-dimensional architecture of membrane-embedded MscS in the closed conformation." J Mol Biol 378(1);55-70. PMID: 18343404
MendozaVargas09: Mendoza-Vargas A, Olvera L, Olvera M, Grande R, Vega-Alvarado L, Taboada B, Jimenez-Jacinto V, Salgado H, Juarez K, Contreras-Moreira B, Huerta AM, Collado-Vides J, Morett E (2009). "Genome-wide identification of transcription start sites, promoters and transcription factor binding sites in E. coli." PLoS One 4(10);e7526. PMID: 19838305
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