Aerolysin and pertussis toxin share a common receptor-binding domain.
We have discovered that the bacterial toxins aerolysin and pertussis toxin share a common domain. This is surprising because the two toxins affect cells in very different ways. The common domain, which we call the APT domain, consists of two three-stranded antiparallel beta-sheets that come together and wrap around a central pair of helices. The APT domain shares a common fold with the C-type lectins and Link modules, and there appears to be a divergent relationship among the three families. One surface region of the APT domain is highly conserved, raising the possibility that the domains have a common function in both proteins. Mutation of one of the conserved surface residues in aerolysin, Tyr61, results in reduced receptor binding and activity, thus providing evidence that the APT domain may be involved in interaction with the toxin's receptor. Structural and biochemical evidence suggests that the APT domain contains a carbohydrate-binding site that can direct the toxins to their target cells.
Rossjohn
J
J
The Ian Potter Foundation Protein Crystallography Laboratory, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
Buckley
J T
JT
Hazes
B
B
Murzin
A G
AG
Read
R J
RJ
Parker
M W
MW
D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D017124:Conserved Sequence; D016208:Databases, Factual; D006801:Humans; D037102:Lectins / Q000737:chemistry; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D037342:Pertussis Toxin; D052899:Pore Forming Cytotoxic Proteins; D011487:Protein Conformation; D017510:Protein Folding; D011956:Receptors, Cell Surface / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014443:Tyrosine; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000737:chemistry* / Q000378:metabolism*
D001427:Bacterial Toxins; D037102:Lectins; D052899:Pore Forming Cytotoxic Proteins; D011956:Receptors, Cell Surface; D014643:Variant Surface Glycoproteins, Trypanosoma; D010566:Virulence Factors, Bordetella; D014443:Tyrosine; C032676:aerolysin; D037342:Pertussis Toxin