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55  structures 1  species 2  interactions 1  sequence 1  architecture

Family: LT-IIB (PF06453)

Summary: Type II heat-labile enterotoxin , B subunit (LT-IIB)

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This is the Wikipedia entry entitled "Heat-labile enterotoxin family". More...

Heat-labile enterotoxin family Edit Wikipedia article

Heat-labile enterotoxin alpha chain
PDB 1s5e EBI.jpg
cholera holotoxin, crystal form 1
Identifiers
SymbolEnterotoxin_a
PfamPF01375
Pfam clanCL0084
InterProIPR001144
SCOPe1lts / SUPFAM
Heat-labile enterotoxin beta chain
PDB 1eei EBI.jpg
cholera toxin b-pentamer complexed with metanitrophenyl-alpha-d-galactose
Identifiers
SymbolEnterotoxin_b
PfamPF01376
InterProIPR001835
SCOPe1lts / SUPFAM
Type II heat-labile enterotoxin , B subunit (LT-IIB)
PDB 1qb5 EBI.jpg
escherichia coli heat labile enterotoxin type iib b-pentamer
Identifiers
SymbolLT-IIB
PfamPF06453
InterProIPR010503
SCOPe1tii / SUPFAM

In molecular biology, the heat-labile enterotoxin family includes Escherichia coli heat-labile enterotoxin (Elt) and cholera toxin (Ctx) secreted by Vibrio cholerae.

Elt is so named because it is inactivated at high temperatures.[1]

Mechanism

The A subunit are transported inside by the pentameric B subunits. It then acts by raising cAMP levels through ADP-ribosylation of the alpha-subunit of a Gs protein leading to the constitutive activation of adenylate cyclase. Elevated cAMP levels stimulate the activation of the CFTR channel thus stimulating secretion of chloride ions and water from the enterocyte into the gut lumen. This ionic imbalance causes watery diarrhea.

In addition to its effects on chloride secretion, which involve the same steps as the effects of cholera toxin, Elt binds additional substrates: lipopolysaccharide on the surface of E. coli cells and A-type blood antigens.[2] The importance of these binding events is not yet known.

Structure

These toxins consist of an AB5 multimer structure, in which a pentamer of B chains has a membrane-binding function and an A chain is needed for enzymatic activity.[3] The B subunits are arranged as a doughnut-shaped pentamer, each subunit participating in ~30 hydrogen bonds and 6 salt bridges with its two neighbours.[3]

The A subunit has a less well-defined secondary structure. It predominantly interacts with the pentamer via the C-terminal A2 fragment, which runs through the charged central pore of the B subunits. A putative catalytic residue in the A1 fragment (Glu112) lies close to a hydrophobic region, which packs two loops together. It is thought that this region might be important for catalysis and membrane translocation.[3]

The structural arrangement of E. coli type I and type II heat-labile enterotoxins are very similar, although they are antigenically distinct.[4]

Origin

The cholera toxin is carried by the CTXφ bacteriophage and may be isolated from plamids. The E. coli LT (elt) is similarly associated with mobile elements, in this case Ent plasmids that can carry LT, ST, or both. Partial insertion sequences (ISs) flanking the elt genes provide extra transmission capabilities by homologous recombination at their inverted repeats.[5] Οβ phage-induced conversion in E. coli has been described as well.[6]

Applications

The B subunits of toxins in this family is relatively harmless on its own. CtxB is routinely used as a neuronal tracer.[7] Elt-IB has been looked into as an adjuvant in trandermal vaccines.[8][1]

References

  1. ^ a b Glenn GM, Flyer DC, Ellingsworth LR, et al. (October 2007). "Transcutaneous immunization with heat-labile enterotoxin: development of a needle-free vaccine patch". Expert Rev Vaccines. 6 (5): 809–19. doi:10.1586/14760584.6.5.809. PMID 17931160.
  2. ^ Mudrak B and Kuehn MJ (2010). "Heat-labile enterotoxin: Beyond GM1 binding". Toxins. 2 (6): 1445–1470. doi:10.3390/toxins2061445. PMC 3153253. PMID 22069646.
  3. ^ a b c Sixma TK, Kalk KH, van Zanten BA, Dauter Z, Kingma J, Witholt B, Hol WG (April 1993). "Refined structure of Escherichia coli heat-labile enterotoxin, a close relative of cholera toxin". J. Mol. Biol. 230 (3): 890–918. doi:10.1006/jmbi.1993.1209. PMID 8478941.
  4. ^ van den Akker F, Sarfaty S, Twiddy EM, Connell TD, Holmes RK, Hol WG (June 1996). "Crystal structure of a new heat-labile enterotoxin, LT-IIb". Structure. 4 (6): 665–78. doi:10.1016/s0969-2126(96)00073-1. PMID 8805549.
  5. ^ Schlor, S.; Riedl, S.; Bla, J.; Reidl, J. (1 January 2000). "Genetic Rearrangements of the Regions Adjacent to Genes Encoding Heat-Labile Enterotoxins (eltAB) of Enterotoxigenic Escherichia coli Strains". Applied and Environmental Microbiology. 66 (1): 352–358. doi:10.1128/AEM.66.1.352-358.2000. PMC 91829.
  6. ^ Takeda, Y; Murphy, JR (January 1978). "Bacteriophage conversion of heat-labile enterotoxin in Escherichia coli". Journal of Bacteriology. 133 (1): 172–7. PMC 221991. PMID 338578.
  7. ^ Pierre-Hervé Luppi. "The Discovery of Cholera-Toxin as a Powerful Neuroanatomical Tool". Retrieved 2011-03-23.
  8. ^ Wagner B, Hufnagl K, Radauer C, et al. (April 2004). "Expression of the B subunit of the heat-labile enterotoxin of Escherichia coli in tobacco mosaic virus-infected Nicotiana benthamiana plants and its characterization as mucosal immunogen and adjuvant". Journal of Immunological Methods. 287 (1–2): 203–15. doi:10.1016/j.jim.2004.02.001. PMID 15099768.

External links

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Type II heat-labile enterotoxin , B subunit (LT-IIB) Provide feedback

Family of B subunits from the type II heat-labile enterotoxin. The B subunits form a pentameric ring, which interacts with one A subunit. Thus, the structural arrangement of type I and type II heat-labile enterotoxins are very similar [1].

Literature references

  1. van den Akker F, Sarfaty S, Twiddy EM, Connell TD, Holmes RK, Hol WG; , Structure 1996;4:665-678.: Crystal structure of a new heat-labile enterotoxin, LT-IIb. PUBMED:8805549 EPMC:8805549


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR010503

These are B subunits from the type II heat-labile enterotoxin. The B subunits form a pentameric ring, which interacts with one A subunit. Thus, the structural arrangement of type I and type II heat-labile enterotoxins are very similar [PUBMED:8805549].

Gene Ontology

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Seed source: Pfam-B_61882 (release 9.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 2
Number in full: 1
Average length of the domain: 122.00 aa
Average identity of full alignment: 100 %
Average coverage of the sequence by the domain: 99.19 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 252.3 252.2
Noise cut-off 21.2 17.9
Model length: 122
Family (HMM) version: 11
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Interactions

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Enterotoxin_a LT-IIB

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the LT-IIB domain has been found. There are 55 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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