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PROSITE documentation PDOC51995

Anthrax toxin lethal factor (ATLF)-like domain profile





Description

The ~200-residue anthrax toxin lethal factor (ATLF)-like domain is found in one or two copies in the following proteins:

  • Bacillus anthracis Lethal factor (LF), a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signaling pathways. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I [1].
  • Bacillus anthracis Edema factor (EF), a key anthrax exotoxin. It has an anthrax protective antigen-binding domain (PABD) and a calcium- and calmodulin-dependent adenylyl cyclase domain, which catalyzes the formation of cAMP and also affects cell signaling and ion fluxes [2].
  • Bacillus cereus Certhrax Toxin, an Anthrax-related ADP-ribosyltransferase. It has two domains, one that binds protective antigen and another that has ADP-ribosyltransferase activity [3].
  • Clostridium difficile Pro-Pro endopeptidase (PPEP-1, previously known as Zmp1), which has a remarkable preference for hydrolyzing a Pro–Pro bond [4,5].
  • Paenibacillus alvei PPEP-2, one of the PPEP-1 homologs [6].

The ATLF-like domain acts either as a metalloprotease domain, forming the M34 family of metalloendopeptidases, (ATLF domain IV, PPEP-1 and 2) or as an anthrax protective antigen-binding domain (PABD) (ATLF domain I and EF and Certhrax PABD).

The ATLF-like domain is composed of a four-stranded β-sheet and a helical bundle backing the β-sheet (see <PDB:A0P>). All catalytically active ATLF-like domains exhibit the conserved sequence motif HEXXH, where the two histidines ligate the catalytic zinc ion, and the glutamic acid acts as catalytic base activating a zinc-bound water molecule for nucleophilic attack on the scissile peptide bond [1,2,3,5,6].

The profile we developed covers the entire ATLF-like domain.

Last update:

March 2022 / First entry.

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Technical section

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

ATLF, PS51995; Anthrax toxin lethal factor (ATLF)-like domain profile  (MATRIX)


References

1AuthorsPannifer A.D. Wong T.Y. Schwarzenbacher R. Renatus M. Petosa C. Bienkowska J. Lacy D.B. Collier R.J. Park S. Leppla S.H. Hanna P. Liddington R.C.
TitleCrystal structure of the anthrax lethal factor.
SourceNature 414:229-233(2001).
PubMed ID11700563
DOI10.1038/n35101998

2AuthorsShen Y. Zhukovskaya N.L. Guo Q. Florian J. Tang W.-J.
TitleCalcium-independent calmodulin binding and two-metal-ion catalytic mechanism of anthrax edema factor.
SourceEMBO. J. 24:929-941(2005).
PubMed ID15719022
DOI10.1038/sj.emboj.7600574

3AuthorsVisschedyk D. Rochon A. Tempel W. Dimov S. Park H.-W. Merrill A.R.
TitleCerthrax toxin, an anthrax-related ADP-ribosyltransferase from Bacillus cereus.
SourceJ. Biol. Chem. 287:41089-41102(2012).
PubMed ID22992735
DOI10.1074/jbc.M112.412809

4AuthorsHensbergen P.J. Klychnikov O.I. Bakker D. van Winden V.J.C. Ras N. Kemp A.C. Cordfunke R.A. Dragan I. Deelder A.M. Kuijper E.J. Corver J. Drijfhout J.W. van Leeuwen H.C.
TitleA novel secreted metalloprotease (CD2830) from Clostridium difficile cleaves specific proline sequences in LPXTG cell surface proteins.
SourceMol. Cell. Proteomics. 13:1231-1244(2014).
PubMed ID24623589
DOI10.1074/mcp.M113.034728

5AuthorsSchacherl M. Pichlo C. Neundorf I. Baumann U.
TitleStructural Basis of Proline-Proline Peptide Bond Specificity of the Metalloprotease Zmp1 Implicated in Motility of Clostridium difficile.
SourceStructure 23:1632-1642(2015).
PubMed ID26211609
DOI10.1016/j.str.2015.06.018

6AuthorsKlychnikov O.I. Shamorkina T.M. Weeks S.D. van Leeuwen H.C. Corver J. Drijfhout J.W. van Veelen P.A. Sluchanko N.N. Strelkov S.V. Hensbergen P.J.
TitleDiscovery of a new Pro-Pro endopeptidase, PPEP-2, provides mechanistic insights into the differences in substrate specificity within the PPEP family.
SourceJ. Biol. Chem. 293:11154-11165(2018).
PubMed ID29794027
DOI10.1074/jbc.RA118.003244



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