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PDBsum entry 2as8
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References listed in PDB file
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Key reference
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Title
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Three-Dimensional structure and ige-Binding properties of mature fully active der p 1, A clinically relevant major allergen.
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Authors
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S.De halleux,
E.Stura,
L.Vanderelst,
V.Carlier,
M.Jacquemin,
J.M.Saint-Remy.
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Ref.
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J Allergy Clin Immunol, 2006,
117,
571-576.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Der p 1 is a 25-kd allergen with cysteine protease activity.
Sensitization to Der p 1 affects a large proportion of individuals with allergy,
resulting in rhinitis, asthma, and/or atopic dermatitis. OBJECTIVE: We
determined the Der p 1 crystallographic structure to understand the
relationships among structure, function, and allergenicity. METHODS: Recombinant
pro-Der p 1 was produced in Pichia pastoris and allowed to mature spontaneously
before purification by a 2-step procedure. Protease activity was checked by
using a fluorogenic peptide substrate. Allergenicity was analysed by IgE binding
assays and basophil activation test. The determination of the 3-dimensional
structure was obtained by X-ray crystallography at 1.9 A resolution. RESULTS:
The recombinant protein is fully active and expresses an allergenicity
equivalent to its natural counterpart. Der p 1 exhibits a cysteine protease fold
typical of the papain family, has a magnesium binding site, and forms dimers
with a large interface. The crystal lattice shows that the dimers are tightly
packed in a compact double layer of proteins. Such an assembly likely exists in
dry fecal pellets, the natural form of allergen exposure, and appears ideal to
interact with cell surface and trigger allergic inflammation. CONCLUSION: We
present here the 3-dimensional structural features of mature fully active Der p
1, one of the main allergens involved in human allergic diseases. This opens the
possibility to evaluate the importance of enzymatic activity in pathology and
possible new therapeutic interventions.
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