Computational study of pH-dependent oligomerization and ligand binding in Alt a 1, a highly allergenic protein with a unique fold

Garrido Arandia, María and Bretones, Jorge and Gómez Casado, C. and Cubells Baeza, Nuria and Díaz Perales, Araceli and Pacios, Luis F. (2015). Computational study of pH-dependent oligomerization and ligand binding in Alt a 1, a highly allergenic protein with a unique fold. "Journal of Computer-Aided Molecular Design", v. 30 (n. 5); pp. 365-379. ISSN 0920-654X. https://doi.org/10.1007/s10822-016-9911-6.

Description

Title: Computational study of pH-dependent oligomerization and ligand binding in Alt a 1, a highly allergenic protein with a unique fold
Author/s:
  • Garrido Arandia, María
  • Bretones, Jorge
  • Gómez Casado, C.
  • Cubells Baeza, Nuria
  • Díaz Perales, Araceli
  • Pacios, Luis F.
Item Type: Article
Título de Revista/Publicación: Journal of Computer-Aided Molecular Design
Date: 2015
ISSN: 0920-654X
Volume: 30
Subjects:
Faculty: Centro de Investigación en Biotecnología y Genómica de Plantas (CBGP) (UPM)
Department: Otro
Creative Commons Licenses: Recognition - No derivative works - Non commercial

Full text

[img]
Preview
PDF - Requires a PDF viewer, such as GSview, Xpdf or Adobe Acrobat Reader
Download (13MB) | Preview

Abstract

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.

More information

Item ID: 41267
DC Identifier: http://oa.upm.es/41267/
OAI Identifier: oai:oa.upm.es:41267
DOI: 10.1007/s10822-016-9911-6
Official URL: http://link.springer.com/article/10.1007/s10822-016-9911-6
Deposited by: Memoria Investigacion
Deposited on: 27 Oct 2016 12:30
Last Modified: 27 Oct 2016 12:30
  • Logo InvestigaM (UPM)
  • Logo GEOUP4
  • Logo Open Access
  • Open Access
  • Logo Sherpa/Romeo
    Check whether the anglo-saxon journal in which you have published an article allows you to also publish it under open access.
  • Logo Dulcinea
    Check whether the spanish journal in which you have published an article allows you to also publish it under open access.
  • Logo de Recolecta
  • Logo del Observatorio I+D+i UPM
  • Logo de OpenCourseWare UPM