Seminario impartido por Héctor García Seisdedos del Instituto de Biología Molecular de Barcelona
About 50% of the proteins of known structure form symmetric complexes. Symmetry confers unique geometric and functional properties, but it also poses a risk. In sickle cell disease, the symmetry of hemoglobin exacerbates the effect of a mutation, triggering its assembly into harmful fibrils. We examined the universality of this mechanism and its relation to protein structure geometry. We introduced point mutations solely to increase the surface hydrophobicity in 12 symmetric complexes. Remarkably, all of them responded by forming supramolecular assemblies in vitro and in vivo upon their expression in S. cerevisiae. We distinguish these assemblies from aggregates because proteins retain a folded structure within them. To mark this difference, we call them “agglomerates”. This new type of in vivo assemblies appears to form readily during evolution, prompting us to investigate how cells interact with them. To this aim we carried out systematic colocalization experiments between yeast >70 yeast chaperones and 12 distinct agglomerates. We also evaluated whether specific knock out backgrounds sensitize cells to the formation of such agglomerates. Through these experiments we explore interaction networks connecting these supramolecular assemblies to the cell protein machinery.
Fecha del seminario: 07/02/2024 12:00
Lugar del seminario: salón de actos IQF
Ponente del seminario: Héctor García Seisdedos
