Project A26N will investigate the ubiquitin switch of MEX3 E3 ubiquitin ligases on rapid mRNA decay by the CCR4-NOT deadenylation complex, with a focus on MEX3C and HLA-A2 mRNA stability in the immune system. We will combine in vitro reconstitution of the system with an integrative structural approach including cryogenic electron microscopy, macromolecular crystallography, crosslinking mass-spectrometry and NMR spectroscopy. Structure guided protein variants will be tested in cells for their protein-protein interaction network and for their functional consequences on HLA-A2 mRNA stability and HLA-A2 surface expression.
