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Event Entry
What and Who
Structural Characterisation of Cross-Reactive Allergens
Andreas Limacher
Department Of Chemistry And Applied Biosciences, ETH Zürich, Switzerland
Max-Planck-Institut für Informatik - AG 3
Talk
AG 1, AG 2, AG 3, AG 4, AG 5
AG Audience
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Date, Time and Location
Wednesday, 2 November 2005
14:00
-- Not specified --
46.1 - MPII
023
Saarbrücken
Abstract
Cyclophilins and thioredoxins of different fungi were identified as
IgE-binding proteins; they trigger allergies. Serum IgE of individuals
sensitised to a certain organism also recognise proteins of other
organisms including human. These proteins are highly conserved and show
cross- and autoreactivity. The aim of this work was to compare the
three-dimensional structures of the fungal allergens and the homologous
human proteins in order to identify shared structural features, so
called B-cell epitopes, which could be responsible for IgE-mediated
cross-reactivity.
A cyclophilin and a thioredoxin of Malassezia sympodialis, a yeast
involved in allergies and long lasting atopic diseases, were expressed,
crystallised, and their structures were solved by X-ray crystallography.
The solvent-accessible surfaces were compared to the homologous human
proteins in order to identify conserved, putative IgE-binding amino
acids. This analysis revealed three conserved, contiguous surface
patches on the cyclophilins and two patches on the thioredoxins.
Mutational studies have to answer the question, whether the defined
patches really represent immunodominant cross-reactive epitopes. In the
future, the modification of B-cell epitopes could result in a safer use
of the modified allergen in immunotherapy.
In addition, a cyclophilin from the mould Aspergillus fumigatus was
crystallised and the structure was solved by the MAD-method.
Surprisingly, the structure revealed dimerisation by 3D domain swapping
representing one of the first proteins with a swapped central domain.
This behaviour has not been observed among homologous cyclophilins,
which all feature a monomeric conformation. Thus, this structure is very
interesting from a structural point of view. The domain swapping might
be a means of biological regulation, since the active site is obstructed
upon dimerisation.
IgE-binding proteins; they trigger allergies. Serum IgE of individuals
sensitised to a certain organism also recognise proteins of other
organisms including human. These proteins are highly conserved and show
cross- and autoreactivity. The aim of this work was to compare the
three-dimensional structures of the fungal allergens and the homologous
human proteins in order to identify shared structural features, so
called B-cell epitopes, which could be responsible for IgE-mediated
cross-reactivity.
A cyclophilin and a thioredoxin of Malassezia sympodialis, a yeast
involved in allergies and long lasting atopic diseases, were expressed,
crystallised, and their structures were solved by X-ray crystallography.
The solvent-accessible surfaces were compared to the homologous human
proteins in order to identify conserved, putative IgE-binding amino
acids. This analysis revealed three conserved, contiguous surface
patches on the cyclophilins and two patches on the thioredoxins.
Mutational studies have to answer the question, whether the defined
patches really represent immunodominant cross-reactive epitopes. In the
future, the modification of B-cell epitopes could result in a safer use
of the modified allergen in immunotherapy.
In addition, a cyclophilin from the mould Aspergillus fumigatus was
crystallised and the structure was solved by the MAD-method.
Surprisingly, the structure revealed dimerisation by 3D domain swapping
representing one of the first proteins with a swapped central domain.
This behaviour has not been observed among homologous cyclophilins,
which all feature a monomeric conformation. Thus, this structure is very
interesting from a structural point of view. The domain swapping might
be a means of biological regulation, since the active site is obstructed
upon dimerisation.
Contact
Francisco Domingues
326
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Roxane Wetzel, 10/28/2005 13:15
Roxane Wetzel, 10/27/2005 18:58
Roxane Wetzel, 10/27/2005 15:26 -- Created document.
Roxane Wetzel, 10/27/2005 18:58
Roxane Wetzel, 10/27/2005 15:26 -- Created document.