Project title

Glycosyltransferase complexes: A structural approach to understand glycosylation and its defects in cancer cells

Glycosylation is the most common and diverse modification of cellular proteins and lipids and crucial for nearly all aspects of multicellular life. It takes place mainly in the Golgi apparatus by the sequential actions of dozens of functionally distinct glycosyltransferases and glycosidases. Very recently, we and others have provided compelling in vivo evidence for a new concept which states that these enzymes function as complexes, and not as monomers as previously thought. This is beneficial for glycosylation, as it provides a simple means to prevent intervention by competing enxymes and thereby to increase the fidelity and speed of glycosylation. This application stems from these discoveries and focuses on resolving crystal structures of selected glycosyltransferase complexes. The structures are essential for detailed understanding on how these enzymes interact and function and how their functions are regulated in normal and misregulated in certain disease state such as cancers.