Beatriz Herguedas Francés and Carlos Vega Gutiérrez participate in an international study, published in the prestigious journal Nature.
An international team led by the MRC Laboratory of Molecular Biology (LMB) in Cambridge (UK), with the participation of Beatriz Herguedas Francés and Carlos Vega Gutiérrez, who are researchers at the University Institute for Research in Biocomputation and Physics of Complex Systems (BIFI) at the University of Zaragoza, has deciphered the structure and function of the GluA3 brain receptor , which plays a key role in neurological diseases such as epilepsy and schizophrenia. The study, published in Nature, shows through electron cryomicroscopy and computational simulations how this receptor adopts a unique architecture among AMPA receptors, with its extracellular domains coupled as a ‘molecular switch’ that allows rapid brain signalling.
Researcher Carlos Vega Gutiérrez spent time in Ingo Greger’s group at the MRC Laboratory of Molecular Biology, where he employed a protein production method developed by Beatriz Herguedas’s group at the BIFI institute. This technique enabled large quantities of GluA3 to be produced in its natural (non-mutated) state and enabling its atomic structure to be resolved by cryo-microscopy.
The structure reveals that the new interfaces harbour mutations linked to epilepsy and schizophrenia, and identifies a unique area in the receptor that could be modulated with drugs. According to Herguedas: “Understanding the unique structure of GluA3 allows us to explain how certain mutations cause disease. In addition, we are beginning to complete the structural puzzle of AMPA receptors, which will allow us to identify new, more specific modulation routes for these receptors that are fundamental for neuronal communication”.
Collaborators: MRC LMB (UK), University of Zaragoza (Spain), Centro Nacional de Biotecnología (CSIC) and University of Texas MD Anderson Cancer Center.
Publication: ‘Architecture, dynamics and biogenesis of GluA3 AMPA glutamate receptors’ (Nature, DOI: 10.1038/s41586-025-09325-z).
