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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 glycosylation structures.(A) Full (largest) glycosylation structure of Fel d 1, shaded boxes indicate saccharides that are absent in the minimal (smallest) glycosylation structure. (B) Fel d 1 structure with full glycan chains attached. Calcium ions are shown as orange spheres, Chain A is shown in yellow, Chain B is shown in blue.
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pone.0132311.g002: Fel d 1 glycosylation structures.(A) Full (largest) glycosylation structure of Fel d 1, shaded boxes indicate saccharides that are absent in the minimal (smallest) glycosylation structure. (B) Fel d 1 structure with full glycan chains attached. Calcium ions are shown as orange spheres, Chain A is shown in yellow, Chain B is shown in blue.

Mentions: The glycosylation pattern of Fel d 1 has been determined by mass spectrometry, revealing a series of possible glycoforms bound to the protein [14]. As observed for other glycosylated proteins, there is a minimal structure to which different oligosaccharides may be added, leading to variation in the glycan moiety, which is limited to the largest glycosylation tree identified. For the present work we employed the extremes of the glycosylation structure, analyzing the largest (or “full glycosylation”) and the smallest (“minimal glycosylation”) structures found by mass spectrometry [14] (Fig 2). Intermediate glycostructures have different numbers of galactose, mannose, and sialic acid residues.


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 glycosylation structures.(A) Full (largest) glycosylation structure of Fel d 1, shaded boxes indicate saccharides that are absent in the minimal (smallest) glycosylation structure. (B) Fel d 1 structure with full glycan chains attached. Calcium ions are shown as orange spheres, Chain A is shown in yellow, Chain B is shown in blue.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4489793&req=5

pone.0132311.g002: Fel d 1 glycosylation structures.(A) Full (largest) glycosylation structure of Fel d 1, shaded boxes indicate saccharides that are absent in the minimal (smallest) glycosylation structure. (B) Fel d 1 structure with full glycan chains attached. Calcium ions are shown as orange spheres, Chain A is shown in yellow, Chain B is shown in blue.
Mentions: The glycosylation pattern of Fel d 1 has been determined by mass spectrometry, revealing a series of possible glycoforms bound to the protein [14]. As observed for other glycosylated proteins, there is a minimal structure to which different oligosaccharides may be added, leading to variation in the glycan moiety, which is limited to the largest glycosylation tree identified. For the present work we employed the extremes of the glycosylation structure, analyzing the largest (or “full glycosylation”) and the smallest (“minimal glycosylation”) structures found by mass spectrometry [14] (Fig 2). Intermediate glycostructures have different numbers of galactose, mannose, and sialic acid residues.

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.