Further information
Dr Georgias Diallinas, University of Athens present this lecture.
Abstract: Despite the fact that high-resolution structures of membrane proteins are now emerging, the hydrophobic and metastable nature of transporters in general make them difficult to study by traditional X-ray crystallography or NMR. In our lab, we use the ascomycete Aspergillus nidulans as a model system to understand basic aspects governing structure-function-specificity relationships in fungal nucleobase transporters. This fungus provides unique genetic, physiological, biochemical and molecular tools for understanding not only how nucleobases transporters recognize their substrates, but also unravel the cellular signals and mechanisms regulating their expression. In this talk, I am going to concentrate on studies concerning structure-function relationships and kinetic modelling of substrate binding in the UapA uric acid-xanthine transporter, the prototype member of the ubiquitous Nucleobase-Ascorbate Transporter (NAT) family. I am going to show how classical and reverse genetics combined with easy kinetic assays led us to unravel the molecular determinants underlying substrate recognition, binding and transport. I will also discuss the possibility of exploiting the Aspergillus system to understand the function and specificity of other NAT members from metazoans, especially the human ascorbate SVCT transporters. Finally, I will also present unpublished data that unmask a novel, previously unnoticed, down-regulation mechanism of UapA by endocytosis and ubiquitination, which is directly related to subtle structure-function relationships, and is thus different from known endocytic pathways controlling transporter turnover.
For more information please contact Dr Bernadette Byrne, b.byrne@imperial.ac.uk or Dr Ernesto Cota, e.cota@imperial.ac.uk.