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224 a.a.
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196 a.a.
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196 a.a.
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110 a.a.
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98 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The crystal structure of pertussis toxin.
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Authors
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P.E.Stein,
A.Boodhoo,
G.D.Armstrong,
S.A.Cockle,
M.H.Klein,
R.J.Read.
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Ref.
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Structure, 1994,
2,
45-57.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Pertussis toxin is an exotoxin of the A-B class produced by
Bordetella pertussis. The holotoxin comprises 952 residues forming six subunits
(five different sequences, S1-S5). It plays an important role in the development
of protective immunity to whooping cough, and is an essential component of new
acellular vaccines. It is also widely used as a biochemical tool to
ADP-ribosylate GTP-binding proteins in the study of signal transduction.
RESULTS: The crystal structure of pertussis toxin has been determined at 2.9 A
resolution. The catalytic A-subunit (S1) shares structural homology with other
ADP-ribosylating bacterial toxins, although differences in the carboxy-terminal
portion explain its unique activation mechanism. Despite its heterogeneous
subunit composition, the structure of the cell-binding B-oligomer (S2, S3, two
copies of S4, and S5) resembles the symmetrical B-pentamers of the cholera toxin
and Shiga toxin families, but it interacts differently with the A-subunit. The
structural similarity is all the more surprising given that there is almost no
sequence homology between B-subunits of the different toxins. Two peripheral
domains that are unique to the pertussis toxin B-oligomer show unexpected
structural homology with a calcium-dependent eukaryotic lectin, and reveal
possible receptor-binding sites. CONCLUSION: The structure provides insight into
the pathogenic mechanisms of pertussis toxin and the evolution of bacterial
toxins. Knowledge of the tertiary structure of the active site forms a rational
basis for elimination of catalytic activity in recombinant molecules for vaccine
use.
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Figure 2.
Figure 2. Stereo views of Cα representations of individual
pertussis toxin subunits, in the same orientation as Figure 1a.
(a)S1, (b)S2, (c)S4, and (d)S5. S3, which is very similar to S2,
is not shown. The amino (N) and carboxyl (C) termini of each
subunit are labelled and the Cα atom of every tenth residue is
numbered. Secondary structure was assigned with DSSP [55]. S1 β
1, 6–11; α1, 15–21; β2, 23–24; α2, 32–37; β3,
50–54; α3, 57–77; β4, 83–92; β5, 97–99, α4,
100–111; α5, 118–127; β6, 129–133; β7, 135–136; β8,
141–150; β9, 155–162; β10, 191–193; β11, 198–199;
α6, 200–205; β12; 225–227; α7, 228–231. S2 and S3
amino-terminal domain: β 1, 27–29; α1, 32–37; α2,
39–48; β2, 54–56; β3, 61–63; β4, 70–72; β5, 84–93.
Carboxy-terminal domain: β6, 100–105; β7, 106–113; β8,
119–125; β9, 128–135; α3, 146–159; β10, 163–173;
β11, 183–191. S4: β1, 6–10; β2, 11–20; β3, 27–36;
β4, 48–55; α1, 63–74; β5, 78–89; β6, 92–102. S5:
β1, 5– 9; β2, 10–20; β3, 23–31; β4, 37–43; α1,
51– 66; β5, 70–74; β6, 84–91. Figure 2. Stereo views
of Cα representations of individual pertussis toxin subunits,
in the same orientation as Figure 1a. (a)S1, (b)S2, (c)S4, and
(d)S5. S3, which is very similar to S2, is not shown. The amino
(N) and carboxyl (C) termini of each subunit are labelled and
the Cα atom of every tenth residue is numbered. Secondary
structure was assigned with DSSP [[4]55]. S1 β 1, 6–11; α1,
15–21; β2, 23–24; α2, 32–37; β3, 50–54; α3, 57–77;
β4, 83–92; β5, 97–99, α4, 100–111; α5, 118–127; β6,
129–133; β7, 135–136; β8, 141–150; β9, 155–162; β10,
191–193; β11, 198–199; α6, 200–205; β12; 225–227;
α7, 228–231. S2 and S3 amino-terminal domain: β 1, 27–29;
α1, 32–37; α2, 39–48; β2, 54–56; β3, 61–63; β4,
70–72; β5, 84–93. Carboxy-terminal domain: β6, 100–105;
β7, 106–113; β8, 119–125; β9, 128–135; α3, 146–159;
β10, 163–173; β11, 183–191. S4: β1, 6–10; β2, 11–20;
β3, 27–36; β4, 48–55; α1, 63–74; β5, 78–89; β6,
92–102. S5: β1, 5– 9; β2, 10–20; β3, 23–31; β4,
37–43; α1, 51– 66; β5, 70–74; β6, 84–91.
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Figure 3.
Figure 3. Stereo view of Cα tracings of PT (blue) and LT (red)
with their A-subunits superimposed. Figure 3. Stereo view of
Cα tracings of PT (blue) and LT (red) with their A-subunits
superimposed.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(1994,
2,
45-57)
copyright 1994.
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