Limits...
An Allergen Portrait Gallery: Representative Structures and an Overview of IgE Binding Surfaces.

Schein CH, Ivanciuc O, Midoro-Horiuti T, Goldblum RM, Braun W - Bioinform Biol Insights (2010)

Bottom Line: Groups of similar sequences are identified for allergenic proteins from diverse sources, and all allergens are classified into a limited number of protein structural families.A gallery of experimental structures selected from the protein classes with the largest number of allergens demonstrate the structural diversity of the allergen universe.Further comparison of these structures and identification of areas that are different from innocuous proteins within the same protein family can be used to identify features specific to known allergens.

View Article: PubMed Central - PubMed

Affiliation: Sealy Center for Structural Biology and Molecular Biophysics.

ABSTRACT
Recent progress in the biochemical classification and structural determination of allergens and allergen-antibody complexes has enhanced our understanding of the molecular determinants of allergenicity. Databases of allergens and their epitopes have facilitated the clustering of allergens according to their sequences and, more recently, their structures. Groups of similar sequences are identified for allergenic proteins from diverse sources, and all allergens are classified into a limited number of protein structural families. A gallery of experimental structures selected from the protein classes with the largest number of allergens demonstrate the structural diversity of the allergen universe. Further comparison of these structures and identification of areas that are different from innocuous proteins within the same protein family can be used to identify features specific to known allergens. Experimental and computational results related to the determination of IgE binding surfaces and methods to define allergen-specific motifs are highlighted.

No MeSH data available.


Allergens in complex with IgE or IgG Fab fragments. Timothy pollen Phl p 2–IgE; bovine milk beta-lactoglobulin Bos d 5–IgE; German cockroach Bla g 2–IgG; birch pollen Bet v 1–IgG; honey bee venom hyaluronidase Api m 2–IgG. Allergens are colored red with epitopes colored yellow, whereas the H and L chains of Fab are colored magenta and cyan, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2964044&req=5

f2-bbi-2010-113: Allergens in complex with IgE or IgG Fab fragments. Timothy pollen Phl p 2–IgE; bovine milk beta-lactoglobulin Bos d 5–IgE; German cockroach Bla g 2–IgG; birch pollen Bet v 1–IgG; honey bee venom hyaluronidase Api m 2–IgG. Allergens are colored red with epitopes colored yellow, whereas the H and L chains of Fab are colored magenta and cyan, respectively.

Mentions: Most of the IgE epitopes that have been elucidated so far are “linear” or “continuous” ASMs as they were defined by probing overlapping synthetic peptides of the allergens for the binding of IgE from the sera of allergic patients. However, the epitopes to which IgE binds most tightly are most commonly formed by residues that become contiguous on the protein surface after folding.5,6,8,63–67 Identifying such “conformational epitopes” is currently a major challenge.17,24,27,48,58,68,69 Experimentally, conformational IgE epitopes can be defined most convincingly by examining the crystal structures of complexes of the allergen and the binding fragments (Fab) of relevant antibodies.66,70–72 However, only five X-ray structures of complexes of allergen–Fab fragments have been determined so far (Fig. 2): the major allergens from Timothy grass pollen Phl p 273 and bovine milk β-lactoglobulin Bos d 571 with recombinant Fab fragments of human IgE; the major allergens from birch pollen Bet v 1,74 bee venom hyaluronidase Api m 2,72 and the major allergen from German cockroach Bla g 2 with monoclonal IgG antibodies66 that were shown in competition assays to bind to or near human IgE epitopes.


An Allergen Portrait Gallery: Representative Structures and an Overview of IgE Binding Surfaces.

Schein CH, Ivanciuc O, Midoro-Horiuti T, Goldblum RM, Braun W - Bioinform Biol Insights (2010)

Allergens in complex with IgE or IgG Fab fragments. Timothy pollen Phl p 2–IgE; bovine milk beta-lactoglobulin Bos d 5–IgE; German cockroach Bla g 2–IgG; birch pollen Bet v 1–IgG; honey bee venom hyaluronidase Api m 2–IgG. Allergens are colored red with epitopes colored yellow, whereas the H and L chains of Fab are colored magenta and cyan, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2964044&req=5

f2-bbi-2010-113: Allergens in complex with IgE or IgG Fab fragments. Timothy pollen Phl p 2–IgE; bovine milk beta-lactoglobulin Bos d 5–IgE; German cockroach Bla g 2–IgG; birch pollen Bet v 1–IgG; honey bee venom hyaluronidase Api m 2–IgG. Allergens are colored red with epitopes colored yellow, whereas the H and L chains of Fab are colored magenta and cyan, respectively.
Mentions: Most of the IgE epitopes that have been elucidated so far are “linear” or “continuous” ASMs as they were defined by probing overlapping synthetic peptides of the allergens for the binding of IgE from the sera of allergic patients. However, the epitopes to which IgE binds most tightly are most commonly formed by residues that become contiguous on the protein surface after folding.5,6,8,63–67 Identifying such “conformational epitopes” is currently a major challenge.17,24,27,48,58,68,69 Experimentally, conformational IgE epitopes can be defined most convincingly by examining the crystal structures of complexes of the allergen and the binding fragments (Fab) of relevant antibodies.66,70–72 However, only five X-ray structures of complexes of allergen–Fab fragments have been determined so far (Fig. 2): the major allergens from Timothy grass pollen Phl p 273 and bovine milk β-lactoglobulin Bos d 571 with recombinant Fab fragments of human IgE; the major allergens from birch pollen Bet v 1,74 bee venom hyaluronidase Api m 2,72 and the major allergen from German cockroach Bla g 2 with monoclonal IgG antibodies66 that were shown in competition assays to bind to or near human IgE epitopes.

Bottom Line: Groups of similar sequences are identified for allergenic proteins from diverse sources, and all allergens are classified into a limited number of protein structural families.A gallery of experimental structures selected from the protein classes with the largest number of allergens demonstrate the structural diversity of the allergen universe.Further comparison of these structures and identification of areas that are different from innocuous proteins within the same protein family can be used to identify features specific to known allergens.

View Article: PubMed Central - PubMed

Affiliation: Sealy Center for Structural Biology and Molecular Biophysics.

ABSTRACT
Recent progress in the biochemical classification and structural determination of allergens and allergen-antibody complexes has enhanced our understanding of the molecular determinants of allergenicity. Databases of allergens and their epitopes have facilitated the clustering of allergens according to their sequences and, more recently, their structures. Groups of similar sequences are identified for allergenic proteins from diverse sources, and all allergens are classified into a limited number of protein structural families. A gallery of experimental structures selected from the protein classes with the largest number of allergens demonstrate the structural diversity of the allergen universe. Further comparison of these structures and identification of areas that are different from innocuous proteins within the same protein family can be used to identify features specific to known allergens. Experimental and computational results related to the determination of IgE binding surfaces and methods to define allergen-specific motifs are highlighted.

No MeSH data available.