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PDBsum entry 3f5v
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References listed in PDB file
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Key reference
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Title
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Crystal structures of mite allergens der f 1 and der p 1 reveal differences in surface-Exposed residues that may influence antibody binding.
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Authors
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M.Chruszcz,
M.D.Chapman,
L.D.Vailes,
E.A.Stura,
J.M.Saint-Remy,
W.Minor,
A.Pomés.
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Ref.
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J Mol Biol, 2009,
386,
520-530.
[DOI no: ]
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PubMed id
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Abstract
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The group 1 mite allergens Der f 1 and Der p 1 are potent allergens excreted by
Dermatophagoides farinae and Dermatophagoides pteronyssinus, respectively. The
human immunoglobulin E antibody responses to the group 1 allergens show more
cross-reactivity than the murine immunoglobulin G antibody responses, which are
largely species specific. Here, we report the crystal structure of the mature
form of Der f 1, which was isolated from its natural source, and a new
high-resolution structure of mature recombinant Der p 1. Unlike Der p 1, Der f 1
is monomeric both in the crystalline state and in solution. Moreover, no metal
binding is observed in the structure of Der f 1 despite the fact that all amino
acids involved in Ca(2+) binding in Der p 1 are completely conserved in Der f 1.
Although Der p 1 and Der f 1 share an extensive sequence identity, comparison of
the crystal structures of both allergens revealed structural features that could
explain the differences in murine IgG and human IgE antibody responses to these
allergens. There are structural differences between Der f 1 and Der p 1 that are
unevenly distributed on the allergens' surfaces. This uneven spatial arrangement
of conserved versus altered residues could explain both the specificity and
cross-reactivity of antibodies against Der f 1 and Der p 1.
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Figure 2.
Fig. 2. (a) Superposition of the Der f 1 (green) and Der p 1
(yellow) active sites. Interactions between residues are marked
with dashed lines, and interatomic distances (see Table 1) are
in Å. (b) Superposition of the putative Der f 1 metal
binding site (green) with the metal binding site observed in the
proDer p 1 (blue; PDB code 1XKG) and mature Der p 1 (yellow)
structures. Residues are numbered according to the Der f 1
sequence. The water molecules coordinating Y^3+ (cyan sphere)
were omitted for the sake of picture clarity. Coordination of
Ca^2+ (black sphere) in the Der p 1 structure (PDB code 3F5V) is
shown using dashed lines. (c) Water molecules (red spheres)
conserved in the Der f 1 (PDB code 3D6S), proDer p 1 (PDB code
1XKG) and mature Der p 1 (PDB code 3F5V) crystal structures.
Black sphere shows the position of the metal ion in the
structure of Der p 1.
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Figure 3.
Fig. 3. (a) The putative dimer formed by mature Der p 1 (PDB
codes 2AS8 and 3F5V). Der p 1 molecules are shown in ribbon
representation, while calcium ions are shown as red spheres. (b)
Tyr166 and Gln167 (Der f 1 numbering) are blocking the catalytic
cleft in a putative dimer of Der p 1. Chain A is shown in
surface representation (green); chain B is shown in blue, while
catalytic Cys35A is shown in orange.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2009,
386,
520-530)
copyright 2009.
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