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DOI no:
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Nat Struct Mol Biol
14:76-84
(2007)
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PubMed id:
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Identification and structural basis of binding to host lung glycogen by streptococcal virulence factors.
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A.L.van Bueren,
M.Higgins,
D.Wang,
R.D.Burke,
A.B.Boraston.
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ABSTRACT
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The ability of pathogenic bacteria to recognize host glycans is often essential
to their virulence. Here we report structure-function studies of previously
uncharacterized glycogen-binding modules in the surface-anchored pullulanases
from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA).
Multivalent binding to glycogen leads to a strong interaction with alveolar type
II cells in mouse lung tissue. X-ray crystal structures of the binding modules
reveal a novel fusion of tandem modules into single, bivalent functional
domains. In addition to indicating a structural basis for multivalent
attachment, the structure of the SpuA modules in complex with carbohydrate
provides insight into the molecular basis for glycogen specificity. This report
provides the first evidence that intracellular lung glycogen may be a novel
target of pathogenic streptococci and thus provides a rationale for the
identification of the streptococcal alpha-glucan-metabolizing machinery as
virulence factors.
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Selected figure(s)
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Figure 2.
(a) T. maritima CBM27. (b) T. maritima CBM41. (c) SpyDX. (d)
SpnDX. The following solutions were spotted on a nitrocellulose
membrane: a1, amylose; a2, amylopectin; a3, pullulan; a4,
dextran; a5, glycogen; b1, oat spelt xylan; b2, arabinogalactan;
b3, pachyman; b4, glycerol; b5, thyroglobulin; c1, fetuin; c2,
asialofetuin; c3, mucin type IS; c4, mucin type II; c5, mucin
type III; d1, heparin; d2, chondroitin sulfate; d3, hyaluronic
acid; d4, aggrecan; d5, proteoglycan. The ability of glycogen to
interact with the nitrocellulose membrane is unknown, which may
account for the weak signal produced in this experiment.
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Figure 5.
(a,b) SpnDX-1 with maltotetraose (a) and SpnDX-2 with
maltotriose modeled (b). Representative electron density map
(blue mesh) is a maximum likelihood^42  [A]-weighted^45
2F[o] – F[c] map contoured at 1.5 (0.30
e^- Å^-3) with phases and F[c]s derived from the final
refined model. Ligand (yellow) and binding site residues (gray)
are shown as sticks. (c,d) Schematics of ligand interactions
with SpnDX-1 (c) and SpnDX-2 (d). (e,f) Structural overlap of
the individual CBM41s, CBM41-1 (e) and CBM41-2 (f), from SpnDX
(blue) and SpyDX (green). Modules are shown as C  traces
and conserved binding site residues are shown as sticks.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2007,
14,
76-84)
copyright 2007.
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Figures were
selected
by an automated process.
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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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C.Montanier,
A.L.van Bueren,
C.Dumon,
J.E.Flint,
M.A.Correia,
J.A.Prates,
S.J.Firbank,
R.J.Lewis,
G.G.Grondin,
M.G.Ghinet,
T.M.Gloster,
C.Herve,
J.P.Knox,
B.G.Talbot,
J.P.Turkenburg,
J.Kerovuo,
R.Brzezinski,
C.M.Fontes,
G.J.Davies,
A.B.Boraston,
and
H.J.Gilbert
(2009).
Evidence that family 35 carbohydrate binding modules display conserved specificity but divergent function.
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Proc Natl Acad Sci U S A, 106,
3065-3070.
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PDB codes:
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J.K.Jeong,
O.Kwon,
Y.M.Lee,
D.B.Oh,
J.M.Lee,
S.Kim,
E.H.Kim,
T.N.Le,
D.K.Rhee,
and
H.A.Kang
(2009).
Characterization of the Streptococcus pneumoniae BgaC protein as a novel surface beta-galactosidase with specific hydrolysis activity for the Galbeta1-3GlcNAc moiety of oligosaccharides.
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J Bacteriol, 191,
3011-3023.
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J.P.Turkenburg,
A.M.Brzozowski,
A.Svendsen,
T.V.Borchert,
G.J.Davies,
and
K.S.Wilson
(2009).
Structure of a pullulanase from Bacillus acidopullulyticus.
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Proteins, 76,
516-519.
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PDB code:
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S.A.Shelburne,
D.B.Keith,
M.T.Davenport,
S.B.Beres,
R.K.Carroll,
and
J.M.Musser
(2009).
Contribution of AmyA, an extracellular alpha-glucan degrading enzyme, to group A streptococcal host-pathogen interaction.
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Mol Microbiol, 74,
159-174.
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I.Santi,
A.Pezzicoli,
M.Bosello,
F.Berti,
M.Mariani,
J.L.Telford,
G.Grandi,
and
M.Soriani
(2008).
Functional characterization of a newly identified group B streptococcus pullulanase eliciting antibodies able to prevent alpha-glucans degradation.
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PLoS ONE, 3,
e3787.
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J.A.Preston,
and
D.H.Dockrell
(2008).
Virulence factors in pneumococcal respiratory pathogenesis.
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Future Microbiol, 3,
205-221.
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J.H.Carlson,
W.M.Whitmire,
D.D.Crane,
L.Wicke,
K.Virtaneva,
D.E.Sturdevant,
J.J.Kupko,
S.F.Porcella,
N.Martinez-Orengo,
R.A.Heinzen,
L.Kari,
and
H.D.Caldwell
(2008).
The Chlamydia trachomatis plasmid is a transcriptional regulator of chromosomal genes and a virulence factor.
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Infect Immun, 76,
2273-2283.
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K.J.Gregg,
R.Finn,
D.W.Abbott,
and
A.B.Boraston
(2008).
Divergent modes of glycan recognition by a new family of carbohydrate-binding modules.
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J Biol Chem, 283,
12604-12613.
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PDB codes:
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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.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
|
219 a.a.
