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The Calcium Goes Meow: Effects of Ions and Glycosylation on Fel d 1, the Major Cat Allergen.

Ligabue-Braun R, Sachett LG, Pol-Fachin L, Verli H - PLoS ONE (2015)

Bottom Line: Since the impact of these Fel d 1 structure modifications on the protein dynamics, physiology and pathology are not well established, the present work employed computational biology techniques to tackle these issues.While conformational effects brought upon by glycosylation were identified, potentially involved in cavity volume regulation, our results indicate that only the central Ca2+ ion remains coordinated to Fel d 1 in biological solutions, impairing its proposed role in modulating phospholipase A2 activity.As these results increase our understanding of Fel d 1 structural biology, they may offer new support for understanding its physiological role and impact into cat-promoted allergy.

View Article: PubMed Central - PubMed

Affiliation: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

ABSTRACT
The major cat allergen, Fel d 1, is a structurally complex protein with two N-glycosylation sites that may be filled by different glycoforms. In addition, the protein contains three putative Ca2+ binding sites. Since the impact of these Fel d 1 structure modifications on the protein dynamics, physiology and pathology are not well established, the present work employed computational biology techniques to tackle these issues. While conformational effects brought upon by glycosylation were identified, potentially involved in cavity volume regulation, our results indicate that only the central Ca2+ ion remains coordinated to Fel d 1 in biological solutions, impairing its proposed role in modulating phospholipase A2 activity. As these results increase our understanding of Fel d 1 structural biology, they may offer new support for understanding its physiological role and impact into cat-promoted allergy.

No MeSH data available.


Fel d 1 Ca2+ binding sites.(A) Fel d 1 crystallographic structure highlighting the location of calcium ions; (B) Lateral Ca2+ binding site A; (C) Interfacial Ca2+ binding site; (D) Lateral Ca2+ binding site B. Proposed coordination interactions based on the crystallographic structure are shown as dashed lines. Calcium ions are shown as orange spheres, water molecules are shown as cyan spheres, Chain A is shown in yellow, Chain B is shown in blue. (the orientation of the boxes is different from the one in (A) for clarity).
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pone.0132311.g001: Fel d 1 Ca2+ binding sites.(A) Fel d 1 crystallographic structure highlighting the location of calcium ions; (B) Lateral Ca2+ binding site A; (C) Interfacial Ca2+ binding site; (D) Lateral Ca2+ binding site B. Proposed coordination interactions based on the crystallographic structure are shown as dashed lines. Calcium ions are shown as orange spheres, water molecules are shown as cyan spheres, Chain A is shown in yellow, Chain B is shown in blue. (the orientation of the boxes is different from the one in (A) for clarity).

Mentions: Among the few components of cat dander that can elicit IgE response, the Fel d 1 protein is considered the most potent [6]. Fel d 1, the major cat allergen, is a dimer of all-helical heterodimers, included in the secretoglobin family [7, 8]. Each dimer in the native heterotetramer is N-glycosylated [9], and crystallographic analyses of recombinant Fel d 1 revealed that each dimer has a cavity, possibly involved in the transport of an unknown molecule [7, 8]. For crystallization, a fused version of the protein was produced, in which chains 1 and 2 are linked, making the original tetramer (or dimer of dimers), a simple dimer of the fused protein [8] (Fig 1).


The Calcium Goes Meow: Effects of Ions and Glycosylation on Fel d 1, the Major Cat Allergen.

Ligabue-Braun R, Sachett LG, Pol-Fachin L, Verli H - PLoS ONE (2015)

Fel d 1 Ca2+ binding sites.(A) Fel d 1 crystallographic structure highlighting the location of calcium ions; (B) Lateral Ca2+ binding site A; (C) Interfacial Ca2+ binding site; (D) Lateral Ca2+ binding site B. Proposed coordination interactions based on the crystallographic structure are shown as dashed lines. Calcium ions are shown as orange spheres, water molecules are shown as cyan spheres, Chain A is shown in yellow, Chain B is shown in blue. (the orientation of the boxes is different from the one in (A) for clarity).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4489793&req=5

pone.0132311.g001: Fel d 1 Ca2+ binding sites.(A) Fel d 1 crystallographic structure highlighting the location of calcium ions; (B) Lateral Ca2+ binding site A; (C) Interfacial Ca2+ binding site; (D) Lateral Ca2+ binding site B. Proposed coordination interactions based on the crystallographic structure are shown as dashed lines. Calcium ions are shown as orange spheres, water molecules are shown as cyan spheres, Chain A is shown in yellow, Chain B is shown in blue. (the orientation of the boxes is different from the one in (A) for clarity).
Mentions: Among the few components of cat dander that can elicit IgE response, the Fel d 1 protein is considered the most potent [6]. Fel d 1, the major cat allergen, is a dimer of all-helical heterodimers, included in the secretoglobin family [7, 8]. Each dimer in the native heterotetramer is N-glycosylated [9], and crystallographic analyses of recombinant Fel d 1 revealed that each dimer has a cavity, possibly involved in the transport of an unknown molecule [7, 8]. For crystallization, a fused version of the protein was produced, in which chains 1 and 2 are linked, making the original tetramer (or dimer of dimers), a simple dimer of the fused protein [8] (Fig 1).

Bottom Line: Since the impact of these Fel d 1 structure modifications on the protein dynamics, physiology and pathology are not well established, the present work employed computational biology techniques to tackle these issues.While conformational effects brought upon by glycosylation were identified, potentially involved in cavity volume regulation, our results indicate that only the central Ca2+ ion remains coordinated to Fel d 1 in biological solutions, impairing its proposed role in modulating phospholipase A2 activity.As these results increase our understanding of Fel d 1 structural biology, they may offer new support for understanding its physiological role and impact into cat-promoted allergy.

View Article: PubMed Central - PubMed

Affiliation: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

ABSTRACT
The major cat allergen, Fel d 1, is a structurally complex protein with two N-glycosylation sites that may be filled by different glycoforms. In addition, the protein contains three putative Ca2+ binding sites. Since the impact of these Fel d 1 structure modifications on the protein dynamics, physiology and pathology are not well established, the present work employed computational biology techniques to tackle these issues. While conformational effects brought upon by glycosylation were identified, potentially involved in cavity volume regulation, our results indicate that only the central Ca2+ ion remains coordinated to Fel d 1 in biological solutions, impairing its proposed role in modulating phospholipase A2 activity. As these results increase our understanding of Fel d 1 structural biology, they may offer new support for understanding its physiological role and impact into cat-promoted allergy.

No MeSH data available.