Research Article: Structural characteristics of lipocalin allergens: Crystal structure of the immunogenic dog allergen Can f 6

Date Published: September 16, 2019

Publisher: Public Library of Science

Author(s): Gina M. Clayton, Janice White, Schuyler Lee, John W. Kappler, Sanny K. Chan, Alexander Wlodawer.

http://doi.org/10.1371/journal.pone.0213052

Abstract

Lipocalins represent the most important protein family of the mammalian respiratory allergens. Four of the seven named dog allergens are lipocalins: Can f 1, Can f 2, Can f 4, and Can f 6. We present the structure of Can f 6 along with data on the biophysical and biological activity of this protein in comparison with other animal lipocalins. The Can f 6 structure displays the classic lipocalin calyx-shaped ligand binding cavity within a central β-barrel similar to other lipocalins. Despite low sequence identity between the different dog lipocalin proteins, there is a high degree of structural similarity. On the other hand, Can f 6 has a similar primary sequence to cat, horse, mouse lipocalins as well as a structure that may underlie their cross reactivity. Interestingly, the entrance to the ligand binding pocket is capped by a His instead of the usually seen Tyr that may help select its natural ligand binding partner. Our highly pure recombinant Can f 6 is able to bind to human IgE (hIgE) demonstrating biological antigenicity.

Partial Text

Analyses over the last 2 decades have revealed that most allergens can be grouped into a few families of proteins[1]. One such family is made up of lipocalins. These are amongst the most important inhalant animal allergens. As far as their functions in their host of origin are concerned, these, depending on the lipocalin involved, include a number of properties such as pheromone transport, prostaglandin synthesis, retinoid binding, odorant binding and cancer cell interactions[1]. Lipocalins are small proteins, usually composed of less than 200 amino acids. In spite of their shared ability to act as allergens they have limited sequence homology with each other, even as low as 20%. Yet for the lipocalins whose structures have been determined, they have a common tertiary structure consisting of an 8 stranded antiparallel beta barrel with a hydrophobic ligand binding pocket[2]. Human sensitization has been identified against lipocalins from cows, guinea pigs, horses, cats, mice, rats[3] and several arthropods[4]. Human sensitization to dogs and cats is a known major risk factor for the development of asthma and allergic rhinitis. Because the prevalence of allergic disease to furry animals unfortunately continues to increase worldwide[5–7], it will be useful to expand our knowledge of the structure and function of the lipocalins that are most often involved in such human diseases.

We present the crystal structure of the dog lipocalin Can f 6 and provide a detailed analysis of the structure including its binding pocket compared to previously reported select lipocalin allergens and its functional ability to bind human IgE. The structure of recombinant Can f 6 show the classic lipocalin calyx tertiary structure as is typically described for proteins in this family. Interesting, Can f 6 has a primary sequence that is more similar to other mammalian lipocalins than to other dog lipocalins suggesting a role for co-sensitization and cross-reactivity.

 

Source:

http://doi.org/10.1371/journal.pone.0213052

 

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