Glycosylation is a fundamental post-translational modification in human cells, and many diseases are associated with incorrect glycosylation. In human, proteins and lipids are often decorated by sialic acid, which create vital "sugar-tags" that cells use to recognize each other. The limiting factor in the sialyation of proteins is the transport of activated sialic acid into Golgi by the action of the CMP-Sialic acid transporter (CST). Since sialyation efficiency affects the therapeutic efficacy of many therapeutic glycoproteins, CST is a promising target for glycoengineering. Indeed, each year there is an increase in the number of FDA approved therapeutic biologics that are glycoproteins.

"By elucidating the atomic structure of CST, we can better understand how sialic acid is transported into Golgi" says David Drew, who was leading the study at Stockholm University. "Indeed, over the course of our investigation we uncovered a novel mutation in human CST that dramatically seems to improve its performance". Although the team’s main goal is to piece together this important biological process, David Drew also acknowledges, that "With this knowledge one has the potential to modify the cells used to produce proteins in the drug market so they can be manufactured with improved sialic acid coverage". It is perhaps fitting that this process was uncovered in Sweden after the naming of "sialic acid" was first introduced by the chemist Gunnar Blix in 1957.

The article " Structural basis for the delivery of activated sialic acid into Golgi for sialyation" is published in the scientific journal Nature Structure and Molecular Biology on May 27th. [https://www.nature.com/articles/s41594-019-0225-y]

Structure of CST in complex with the nucleotide CMP, which is the main determinant for bringing sialic acid into Golgi.