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

PLoS One. 2015 Jul 2;10(7):e0132311. doi: 10.1371/journal.pone.0132311. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Calcium / analysis*
  • Calcium / physiology
  • Cats / immunology
  • Cats / metabolism*
  • Dimerization
  • Glycoproteins / chemistry*
  • Glycoproteins / metabolism
  • Glycosylation
  • Hydrogen Bonding
  • Ligands
  • Models, Molecular
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • N-Acetylneuraminic Acid / chemistry
  • Phospholipases A2 / metabolism
  • Polychlorinated Biphenyls / metabolism
  • Progesterone / metabolism
  • Protein Conformation
  • Protein Processing, Post-Translational*
  • Testosterone / metabolism

Substances

  • Glycoproteins
  • Ligands
  • Testosterone
  • Progesterone
  • Polychlorinated Biphenyls
  • Phospholipases A2
  • Fel d 1 protein, Felis domesticus
  • N-Acetylneuraminic Acid
  • Calcium

Grants and funding

This work was supported by CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), CAPES (Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior), FAPERGS (Fundação de Amparo àPesquisa do Estado do Rio Grande do Sul), and FACEPE (Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco, grant number APQ-0398-1.06/13).