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PROSITE documentation PDOC51208

Autotransporter beta-domain profile





Description

Among the pathways that Gram-negative bacteria have evolved to secrete proteins to the surface or the extracellular milieu, autotransporter protein secretion pathway (type Va, AT-1 or TC 1.B.12), is one of the simplest secretion mechanisms, and is widely distributed, especially in pathogenic bacteria [1,2,3,E1]. As implied by their name, autotransporter (AT) proteins contain all the necessary determinants for translocation across the outer membrane within their own polypeptide. They have a modular structure consisting of an N-terminal signal peptide, followed by a "passenger" domain, and by a C-terminal module called the "translocation unit", which consists of a short linker region with an α-helical secondary structure and a β-domain of 250 to 300 amino acid residues [2,3].

Such a structure is shown in the following schematic representation:

                                                +-- translocation unit --+
                                                |                        |
  +--+------------------------------------------+-------+----------------+
  |SP|            passenger domain              |linker |  beta-domain   |
  +--+------------------------------------------+-------+----------------+
  'SP': signal peptide;

While the translocation units of ATs are highly homologous, the passenger domains are very diverse. To date, all characterized passenger domains have been implicated in virulence by displaying enzymatic activity (protease, peptidase, lipase and esterase); mediating actin-promoted bacterial motility; acting as adhesins, immunomodulatory proteins, toxins or cytotoxins, permitting the maturation of other virulence proteins. ATs are present only in the eubacteria and are most prevalent in Proteobacteria, including α-, β-, γ-, and epsilon-Proteobacteria classes [2].

At the cell surface, the precursors of many AT proteins may undergo a proteolytic cleavage in the course of secretion, which results in their separation into two polypeptides, the β-domain in the outer membrane and the passenger protein exposed at the surface or released into the milieu. The cleavage is mediated by the integral serine protease active sites of the AT, present in the passenger domain or by a variety of proteases. But the passenger domain is not necessarily cleaved and may also remain intact as a large protein with a membrane-bound C-terminal domain and an N-terminal domain extending into the external milieu [2,3].

One model for AT secretion suggests that following the Sec-dependent export across the inner membrane, the β-domain inserts into the outer membrane in an anti-parallel β-barrel structure that forms a pore, in the outer membrane, through which the passenger domain is translocated to the bacterial surface in an unfolded form [2,3].

The 3D structure of translocation unit of NalP from Neisseria meningitides reveals a 12-stranded anti-parallel β-barrel with a hydrophilic pore of 10 X 12.5 angstroms (see <PDB:1UYN>) [4], which is consistent with this model. However, it has been reported that the purified C-terminal part of IgA1 protease from Neisseria gonorroheae forms an oligomeric ring-like complex containing a central hydrophilic channel from which the folded passenger domains with a diameter of ~2 nm are secreted [5]. Recently an alternative model was proposed in which the passenger domain is secreted through a pore formed by the omp85 complex, a component of the general machinery for the assembly of outer membrane proteins, rather than through a pore by the translocation unit [4].

Some other proteins known to belong to this family are listed below:

  • Serratia marcescens serine protease ssp.
  • Pasteurella haemolytica serotype 1-specific antigen ssa1.
  • Helicobacter pylori vacuolating cytotoxin vacA.
  • Escherichia coli adhesin aidA.
  • Shigella flexneri outer membrane protein icsA.
  • Escherichia coli antigen ag43.
  • Escherichia coli adhesin/invasin tibA.
  • Salmonella typhimurium adhesin shdA.
  • Haemophilus influenzae adhesion and penetration protein hap.
  • Neisseria meningitidis adhesion and penetration protein app.
  • Escherichia coli temperature-sensitive hemagglutinin tsh.
  • Shigella flexneri serine protease sepA.
  • Escherichia coli serine protease espC.
  • Escherichia coli serine protease espP.
  • Escherichia coli serine protease pet.
  • Escherichia coli serine protease pic.
  • Shigella flexneri serine protease sigA.
  • Escherichia coli O6 serine protease sat.
  • Escherichia coli vacuolating autotransporter toxin vat.
  • Bordetella pertussis brkA.
  • Bordetella pertussis pertactin.
  • Bordetella pertussis tracheal colonization factor tcfA.
  • Chlamydia trachomatis polymorphic membrane protein pmpD.
  • Rickettsia rickettsii outer membrane protein rompA.
  • Rickettsia rickettsii outer membrane protein rompB.
  • Pseudomonas aeruginosa esterase estA.
  • Salmonella typhimurium outer membrane esterase apeE.
  • Photorhabdus luminescens lipase lip-1.
  • Moraxella catarrhalis esterase mcaP.
  • Helicobacter pylori adhesin babA.
  • Helicobacter pylori adhesin sabA.
  • Actinobacillus actinomycetemcomitans adhesin aae.
  • Pasteurella multocida sialidase NanB.

The profile we developed covers the entire β-domain.

Last update:

May 2006 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

AUTOTRANSPORTER, PS51208; Autotransporter beta-domain profile  (MATRIX)


References

1AuthorsLoveless B.J. Saier M.H. Jr.
TitleA novel family of channel-forming, autotransporting, bacterial virulence factors.
SourceMol. Membr. Biol. 14:113-123(1997).
PubMed ID9394291

2AuthorsHenderson I.R. Navarro-Garcia F. Desvaux M. Fernandez R.C. Ala'Aldeen D.
TitleType V protein secretion pathway: the autotransporter story.
SourceMicrobiol. Mol. Biol. Rev. 68:692-744(2004).
PubMed ID15590781
DOI10.1128/MMBR.68.4.692-744.2004

3AuthorsJacob-Dubuisson F. Fernandez R. Coutte L.
TitleProtein secretion through autotransporter and two-partner pathways.
SourceBiochim. Biophys. Acta 1694:235-257(2004).
PubMed ID15546669
DOI10.1016/j.bbamcr.2004.03.008

4AuthorsOomen C.J. van Ulsen P. van Gelder P. Feijen M. Tommassen J. Gros P.
TitleStructure of the translocator domain of a bacterial autotransporter.
SourceEMBO J. 23:1257-1266(2004).
PubMed ID15014442
DOI10.1038/sj.emboj.7600148

5AuthorsVeiga E. de Lorenzo V. Fernandez L.A.
TitleStructural tolerance of bacterial autotransporters for folded passenger protein domains.
SourceMol. Microbiol. 52:1069-1080(2004).
PubMed ID15130125
DOI10.1111/j.1365-2958.2004.04014.x;

E1Sourcehttp://www.tcdb.org/tcdb/index.php?tc=1.B.12



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