KDEL Receptor Stuctural Determination & Biochemical Characterisation (360G-Wellcome-109133_Z_15_A)

This project aims to characterise the KDEL receptor (KDELR) structurally, biochemically and biophysically. The KDELR is a membrane protein resident in the cis-golgi, where it binds the K-D-E-L amino-acid motif present on resident ER proteins, which have been transported to the Golgi via bulk flow. Once KDELR binds cargo, it initiates transport back to the ER via COPI mediated vesicles, where it releases its cargo, ostensibly because of the differing pH. The molecular mechanisms concerning the actions of the KDELR are largely elusive and would be greatly aided by the structural determination of the KDELR, as well as the structures and characterisations of its interactions with native cargos. Furthermore, KDELR has been predicted to be a GPCR, but does not appear to share homology with proteins in the family. However, distant homology to the SWEET family of sugar transporters has been found, suggesting these ‘receptors’ are in fact transporter like proteins. Furthermore, this project has the potential to involve live cell imaging experiments (in collaboration with Prof. Francis Barr) to test hypothesis borne from the structural and biochemical data.