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PDBsum entry 2o2l
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98 a.a.
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(+ 3 more)
103 a.a.
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PDB id:
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Toxin
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Title:
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Crystal structure of human heat-labile enterotoxin in complex with a blood group a antigen analog
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Structure:
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Heat-labile enterotoxin b chain. Chain: d, e, f, g, h, i, j, k, l, m. Synonym: lt-b, human, lth-b. Engineered: yes
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Source:
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Escherichia coli. Organism_taxid: 562. Expressed in: vibrio cholerae. Expression_system_taxid: 666.
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Resolution:
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2.53Å
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R-factor:
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0.184
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R-free:
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0.237
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Authors:
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A.Holmner,G.Askarieh,M.Okvist,U.Krengel
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Key ref:
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A.Holmner
et al.
(2007).
Blood group antigen recognition by Escherichia coli heat-labile enterotoxin.
J Mol Biol,
371,
754-764.
PubMed id:
DOI:
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Date:
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30-Nov-06
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Release date:
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14-Aug-07
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PROCHECK
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Headers
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References
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DOI no:
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J Mol Biol
371:754-764
(2007)
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PubMed id:
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Blood group antigen recognition by Escherichia coli heat-labile enterotoxin.
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A.Holmner,
G.Askarieh,
M.Okvist,
U.Krengel.
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ABSTRACT
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In a number of bacterial infections, such as Helicobacter pylori, Campylobacter
jejuni and Vibrio cholerae infections, a correlation between the severity of
disease and blood group phenotype of infected individuals has been observed. In
the present investigation, we have studied the molecular basis of this effect
for enterotoxigenic Escherichia coli (ETEC) infections. ETEC are non-invasive
bacteria, which act through second messenger pathways to cause diarrhea. It has
been suggested that the major virulence factor of ETEC from human isolates, i.e.
the human heat-labile enterotoxin (hLT), recognizes certain blood group
epitopes, although the molecular basis of blood group antigen recognition is
unknown. The 2.5 A crystal structure of the receptor-binding B-subunit of hLT in
complex with the blood group A antigen analog
GalNAcalpha3(Fucalpha2)Galbeta4(Fucalpha3)Glcbeta provides evidence of a
previously unknown binding site in the native toxin. The structure reveals the
molecular interactions underlying blood group antigen recognition and suggests
how this protein can discriminate between different blood group epitopes. These
results support the previously debated role of hLT in the blood group dependence
of ETEC infections. Similar observations regarding the closely related cholera
toxin in V. cholera infections are also discussed.
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Selected figure(s)
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Figure 1.
Figure 1. (a) Surface representation of the hLT B-pentamer.
The blood group A antigen analog
GalNAcα3(Fucα2)Galβ4(Fucα3)Glcβ is shown in red stick
representation. A model of the GM1 pentasaccharide (black) is
depicted for comparison. (b) Well-defined electron density
(2F[o]−F[c] map, at 1σ) of the pentasaccharide, at the
interface of two B-subunits (in green and blue, respectively)
The Figure was generated with PyMOL: DeLano, W.L.
[http://www.pymol.org].
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Figure 2.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2007,
371,
754-764)
copyright 2007.
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Figures were
selected
by the author.
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In this work, we have identified and characterized a second receptor binding site in native human heat-labile enterotoxin (hLT). The structure explains how the toxin can discriminate between different blood group antigens and strengthens the hypothesis hat hLT, and possibly cholera toxin, are responsible for the blood group dependence observed for cholera and ETEC infections.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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B.Mudrak,
and
M.J.Kuehn
(2010).
Specificity of the type II secretion systems of enterotoxigenic Escherichia coli and Vibrio cholerae for heat-labile enterotoxin and cholera toxin.
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J Bacteriol,
192,
1902-1911.
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C.Ulgheri,
B.Paganini,
and
F.Rossi
(2010).
Antisecretory factor as a potential health-promoting molecule in man and animals.
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Nutr Res Rev,
23,
300-313.
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L.Jansson,
J.Angström,
M.Lebens,
and
S.Teneberg
(2010).
No direct binding of the heat-labile enterotoxin of Escherichia coli to E. coli lipopolysaccharides.
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Glycoconj J,
27,
171-179.
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M.Watanabe,
H.Kinoshita,
M.Nitta,
R.Yukishita,
Y.Kawai,
K.Kimura,
N.Taketomo,
Y.Yamazaki,
Y.Tateno,
K.Miura,
A.Horii,
H.Kitazawa,
and
T.Saito
(2010).
Identification of a new adhesin-like protein from Lactobacillus mucosae ME-340 with specific affinity to the human blood group A and B antigens.
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J Appl Microbiol,
109,
927-935.
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B.Mudrak,
D.L.Rodriguez,
and
M.J.Kuehn
(2009).
Residues of heat-labile enterotoxin involved in bacterial cell surface binding.
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J Bacteriol,
191,
2917-2925.
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C.Sisu,
A.J.Baron,
H.M.Branderhorst,
S.D.Connell,
C.A.Weijers,
R.de Vries,
E.D.Hayes,
A.V.Pukin,
M.Gilbert,
R.J.Pieters,
H.Zuilhof,
G.M.Visser,
and
W.B.Turnbull
(2009).
The influence of ligand valency on aggregation mechanisms for inhibiting bacterial toxins.
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Chembiochem,
10,
329-337.
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J.Flores,
and
P.C.Okhuysen
(2009).
Genetics of susceptibility to infection with enteric pathogens.
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Curr Opin Infect Dis,
22,
471-476.
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A.Imberty,
and
A.Varrot
(2008).
Microbial recognition of human cell surface glycoconjugates.
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Curr Opin Struct Biol,
18,
567-576.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
