Structural, Functional, and Immunological Characterization of Profilin Panallergens Amb a 8, Art v 4, and Bet v 2*
- Lesa R. Offermann‡,§,
- Caleb R. Schlachter‡,
- Makenzie L. Perdue‡,
- Karolina A. Majorek¶,
- John Z. He‡,
- William T. Booth‡,
- Jessica Garrett‡,
- Krzysztof Kowal‖,** and
- Maksymilian Chruszcz‡1
- From the ‡Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208,
- the §Department of Chemistry, Davidson College, Davidson, North Carolina 28035,
- the ¶Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908, and
- the Departments of ‖Allergology and Internal Medicine and
- **Experimental Allergology and Immunology, Medical University of Bialystok, Bialystok 15-276, Poland
- ↵1 To whom correspondence should be addressed: Dept. of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208. Tel.: 803-777-7399; Fax: 803-777-9521; E-mail: chruszcz{at}mailbox.sc.edu.
Abstract
Ragweed allergens affect several million people in the United States and Canada. To date, only two ragweed allergens, Amb t 5 and Amb a 11, have their structures determined and deposited to the Protein Data Bank. Here, we present structures of methylated ragweed allergen Amb a 8, Amb a 8 in the presence of poly(l-proline), and Art v 4 (mugwort allergen). Amb a 8 and Art v 4 are panallergens belonging to the profilin family of proteins. They share significant sequence and structural similarities, which results in cross-recognition by IgE antibodies. Molecular and immunological properties of Amb a 8 and Art v 4 are compared with those of Bet v 2 (birch pollen allergen) as well as with other allergenic profilins. We purified recombinant allergens that are recognized by patient IgE and are highly cross-reactive. It was determined that the analyzed allergens are relatively unstable. Structures of Amb a 8 in complex with poly(l-proline)10 or poly(l-proline)14 are the first structures of the plant profilin in complex with proline-rich peptides. Amb a 8 binds the poly(l-proline) in a mode similar to that observed in human, mouse, and P. falciparum profilin·peptide complexes. However, only some of the residues that form the peptide binding site are conserved.
- allergen
- allergy
- crystal structure
- epitope mapping
- protein stability
- IgE binding
- peptide binding
- pollen
Footnotes
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↵* This work was supported in part by an ASPIRE III grant from the Office of the Vice President of Research at the University of South Carolina, and by the NIAID of the National Institutes of Health under Award Number R01AI077653. Partial support was also obtained from Medical University of Bialystok, Poland. The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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The atomic coordinates and structure factors (codes 5EM1, 5EV0, 5EVE, and 5EM0) have been deposited in the Protein Data Bank (http://wwpdb.org/).
- Received April 19, 2016.
- Revision received May 24, 2016.
- © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
