Limits...
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: 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.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.


Related in: MedlinePlus

Root mean square fluctuations (RMSF) measured for different force field simulations of Fel d 1.Color coding: Simulations without Ca+2 ions (black), simulations with Ca+2 ions (red).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4489793&req=5

pone.0132311.g005: Root mean square fluctuations (RMSF) measured for different force field simulations of Fel d 1.Color coding: Simulations without Ca+2 ions (black), simulations with Ca+2 ions (red).

Mentions: The MD simulated systems were generally stable (Fig 4) and had no difference regarding their stability with or without Ca2+ for simulations under AMBER and CHARMM force fields. In the simulations performed under GROMOS force field, however, there was a slight difference between metal-bound and metal free conditions combined with noticeable difference in stability in comparison with the other force fields. (Fig 4). Regarding local flexibility, we observed little differences between calcium-free and calcium-bound system (Fig 5).


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)

Root mean square fluctuations (RMSF) measured for different force field simulations of Fel d 1.Color coding: Simulations without Ca+2 ions (black), simulations with Ca+2 ions (red).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132311.g005: Root mean square fluctuations (RMSF) measured for different force field simulations of Fel d 1.Color coding: Simulations without Ca+2 ions (black), simulations with Ca+2 ions (red).
Mentions: The MD simulated systems were generally stable (Fig 4) and had no difference regarding their stability with or without Ca2+ for simulations under AMBER and CHARMM force fields. In the simulations performed under GROMOS force field, however, there was a slight difference between metal-bound and metal free conditions combined with noticeable difference in stability in comparison with the other force fields. (Fig 4). Regarding local flexibility, we observed little differences between calcium-free and calcium-bound system (Fig 5).

Bottom Line: 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.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.


Related in: MedlinePlus