X-ray crystal structures of birch pollen profilin and Phl p 2

Alexander A. Fedorov, Tanja Ball, Rudolf Valenta, Steven C. Almo

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background: Type 1 allergy affects 20% of industrialized populations and thus represents a major health care issue. The symptoms of type 1 allergy, which include rhinitis, conjunctivitis, dermatitis and asthma, are elicited by the crosslinking of IgE receptors through polyvalent allergens. A detailed understanding of the cell surface phenomena and the rational development of new therapies require high-resolution structural information. Methods: The structures of two widespread allergens, birch pollen profilin (BPP) and Phl p 2 have been solved by multiple isomorphous replacement. Refinements are underway to 2.4 and 2.0 Å, respectively. In addition, the IgE-reactive epitopes of BPP where identified by screening an epitope expression library with the serum IgE of an allergic individual. Results: BPP exhibits an α/β-fold which is similar to the mammalian and amoeba profilins. The structure of Phl p 2 is a compact eight-stranded β-barrel. Screening an epitope library of BPP identified three major epitopic regions involved in IgE binding, including the amino and carboxy-terminal α-helices. These regions also interact with the physiologically relevant ligands of profilin, actin and proline-rich peptides. Conclusions: The distribution of IgE-binding sites on BPP allows for the productive interaction with IgE antibodies of different epitope specificities required for efficient signal transduction. These epitopes correspond to the most highly conserved regions of the profilin molecule and thus provide the molecular basis for allergen cross-sensitivity. Due to steric considerations, the involvement of these epitopic regions in the binding of physiologically relevant profilin ligands indicates that the native profilin is the species responsible for eliciting the allergic response. A comparison of the BPP and Phl p 2 structures shows that there is no preference for secondary structural elements in the allergic response. The detailed chemical and physical description of the major reactive epitopes provides a data base for the design of tight-binding monovalent ligands which can prevent receptor aggregation and thereby reduce the allergic response.

Original languageEnglish (US)
Pages (from-to)109-113
Number of pages5
JournalInternational Archives of Allergy and Immunology
Volume113
Issue number1-3
StatePublished - 1997

Fingerprint

Profilins
Betula
Pollen
X-Rays
Epitopes
Immunoglobulin E
Allergens
Ligands
Hypersensitivity
Receptor Aggregation
IgE Receptors
Amoeba
Conjunctivitis
Dermatitis
Rhinitis
Proline
Actins
Signal Transduction

Keywords

  • Allergen
  • Crystallography
  • Epitope
  • Phl p 2
  • Profilin
  • Structure

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

X-ray crystal structures of birch pollen profilin and Phl p 2. / Fedorov, Alexander A.; Ball, Tanja; Valenta, Rudolf; Almo, Steven C.

In: International Archives of Allergy and Immunology, Vol. 113, No. 1-3, 1997, p. 109-113.

Research output: Contribution to journalArticle

Fedorov, Alexander A. ; Ball, Tanja ; Valenta, Rudolf ; Almo, Steven C. / X-ray crystal structures of birch pollen profilin and Phl p 2. In: International Archives of Allergy and Immunology. 1997 ; Vol. 113, No. 1-3. pp. 109-113.
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