Abstract

Sialylation reactions take place in the lumen of the Golgi apparatus where sialyltransferases (STs) decorate glycan moieties of both the cell surfaces associated and secreted proteins and lipids with sialic acids (Sia) predominantly, but not exclusively employing, CMP-Neu5Ac as donor substrate. Because of its physical and chemical properties, CMP-Neu5Ac is unable to diffuse across the Golgi membrane and must be translocated from the cell cytosol into the lumen of the Golgi apparatus. Such translocation is performed by the CMP-Sia transporter, a member of an evolutionary conserved family of proteins together referred to as nucleotide sugar transporters. Although several nucleotide sugar transporters, including the CMP-Sia transporter, have been biochemically characterized over the last 30 years, the lack of a three-dimensional structure of any nucleotide sugar transporter requires alternative approaches to elucidating the structure-function relationship of this class of protein. We describe in this chapter the latest data reporting the elucidation of CMP-Sia transporter structurefunction relationship.