Observatorio de I+D+i UPM

Memorias de investigación
Research Publications in journals:
Computational study of pH-dependent oligomerization and ligand binding in Alt a 1, a highly allergenic protein with a unique fold
Research Areas
  • Natural sciences and health sciences,
  • Cell culture,
  • Molecular, cellular and genetic biology,
  • Biological sciences,
  • Biology,
  • Biological engineering
Alt a 1 is a highly allergenic protein from Alternaria fungi responsible for several respiratory diseases. Its crystal structure revealed a unique ?-barrel fold that defines a new family exclusive to fungi and forms a symmetrical dimer in a butterfly-like shape as well as tetramers. Its biological function is as yet unknown but its localization in cell wall of Alternaria spores and its interactions in the onset of allergy reactions point to a function to transport ligands. However, at odds with binding features in ?-barrel proteins, monomeric Alt a 1 seems unable to harbor ligands because the barrel is too narrow. Tetrameric Alt a 1 is able to bind the flavonoid quercetin, yet the stability of the aggregate and the own ligand binding are pH-dependent. At pH 6.5, which Alt a 1 would meet when secreted by spores in bronchial epithelium, tetramer-quercetin complex is stable. At pH 5.5, which Alt a 1 would meet in apoplast when infecting plants, the complex breaks down. By means of a combined computational study that includes docking calculations, empirical pKa estimates, Poisson?Boltzmann electrostatic potentials, and Molecular Dynamics simulations, we identified a putative binding site at the dimeric interface between subunits in tetramer. We propose an explanation on the pH-dependence of both oligomerization states and protein?ligand affinity of Alt a 1 in terms of electrostatic variations associated to distinct protonation states at different pHs. The uniqueness of this singular protein can thus be tracked in the combination of all these features.
Journal of Computer-Aided Molecular Design
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  • Autor: Maria Garrido Arandia (UPM)
  • Autor: Jorge Bretones (Department of Biotechnology and Centre for Plant Genomics and Biotechnology (CBGP), Technical University of Madrid)
  • Autor: Cristina Gómez Casado (Department of Biotechnology and Centre for Plant Genomics and Biotechnology (CBGP), Technical University of Madrid Immunology Section, Department of Experimental Medical Sciences, Lund University)
  • Autor: Nuria Cubells Baeza (UPM)
  • Autor: Araceli Diaz Perales (UPM)
  • Autor: Luis Fernandez Pacios (UPM)
Research Group, Departaments and Institutes related
  • Creador: Grupo de Investigación: Biotecnología Vegetal
  • Departamento: Sistemas y Recursos Naturales
S2i 2020 Observatorio de investigación @ UPM con la colaboración del Consejo Social UPM
Cofinanciación del MINECO en el marco del Programa INNCIDE 2011 (OTR-2011-0236)
Cofinanciación del MINECO en el marco del Programa INNPACTO (IPT-020000-2010-22)