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PDBsum entry 2kc0
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Protein binding
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PDB id
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2kc0
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References listed in PDB file
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Key reference
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Title
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Solution structure of the factor h-Binding protein, A survival factor and protective antigen of neisseria meningitidis.
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Authors
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F.Cantini,
D.Veggi,
S.Dragonetti,
S.Savino,
M.Scarselli,
G.Romagnoli,
M.Pizza,
L.Banci,
R.Rappuoli.
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Ref.
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J Biol Chem, 2009,
284,
9022-9026.
[DOI no: ]
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PubMed id
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Abstract
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Factor H-binding protein is a 27-kDa lipoprotein of Neisseria meningitidis
discovered while screening the bacterial genome for vaccine candidates. In
addition to being an important component of a vaccine against meningococcus in
late stage of development, the protein is essential for pathogenesis because it
allows the bacterium to survive and grow in human blood by binding the human
complement factor H. We recently reported the solution structure of the
C-terminal domain of factor H-binding protein, which contains the immunodominant
epitopes. In the present study, we report the structure of the full-length
molecule, determined by nuclear magnetic resonance spectroscopy. The protein is
composed of two independent barrels connected by a short link. Mapping the
residues recognized by monoclonal antibodies with bactericidal or factor H
binding inhibition properties allowed us to predict the sites involved in the
function of the protein. The structure therefore provides the basis for
designing improved vaccine molecules.
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Figure 1.
A, topology diagram of the fHbp protein. The α-helices are
represented by sky blue cylinders, and the β-strands are cyan
arrows. N-term, N terminus; C-term, C terminus. B, ribbon
diagram of fHbp. Secondary structure elements are shown.
β-strands of the N-terminal domain are shown in cyan and
helices are shown in red, whereas β-strands of fHbpC are shown
in blue. C, the side chains of the hydrophobic residues involved
in interdomains contacts are shown as sticks in red, and pink.
Contact surfaces are also reported. The other hydrophobic
residues are shown in blue. The charged residues are shown in
green. The backbone is shown as a ribbon.
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Figure 2.
A, variability profile of the three fHbp variants. Conserved
amino acids are colored in blue, conservative substitutions are
colored in gray, and variable amino acids are colored in green.
B, distribution of amino acids recognized by monoclonal
antibodies (Mabs) raised against v.1 (purple) and v.2/v.3
(green). C and D, molecular areas recognized by the bactericidal
pairs of monoclonal antibodies against v.1 (orange) and v.2
(gold) (11). E, molecular distribution of fHbp residues
recognized by monoclonal antibodies inhibiting (red), partially
inhibiting (orange), and not inhibiting (green) the fH binding
(11).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2009,
284,
9022-9026)
copyright 2009.
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