Rebekka Wild How do proteins choose their glycosaminoglycan chains?

Glycosaminoglycans, essential protein accessories 

A large number of proteins called proteoglycans are found on the surface of animal and human cells. They allow the cells to respond to interactions with the surrounding environment, including messenger molecules (such as inflammation molecules), pathogens (such as viruses) and other proteins on the same cell or on neighbouring ones. Glycosaminoglycans (GAGs), long chains of sugars to which proteoglycans are attached, allow them to perform these functions. Two examples of GAGs are heparan sulphate and chondroitin sulphate, which attach to their target proteins when the proteins are being manufactured.

The synthesis of glycosaminoglycans 

Once the proteins have been synthesised following precise instructions in the genetic code, they must be folded into the correct shape and modified (by adding GAGs, for example) to become operational proteoglycans. This stage takes place in a cell compartment called the Golgi apparatus. At a specific spot in the protein, the addition of the first building blocks is common to all GAGs. However, the nature of the protein will determine which chain will be attached at the next stage: either a heparan sulphate chain or a chondroitin sulphate chain. The synthesis of each GAG requires specific molecular machinery. The information to know which GAG to make must be contained somewhere in the target protein, but where? What decides which molecular machines need to be set up to generate either a heparan sulphate chain or a chondroitin sulphate chain?

Who is in charge of making decisions? 

Although the molecular machines involved in synthesising heparan sulphates and chondroitin sulphates are well known, much remains to be understood about how they work. Rebekka Wild and her team at the Institut de Biologie Structurale in Grenoble will study in detail the machines responsible for producing the two GAGs to gain a better understanding of the differences between them. The team will be able to observe the entire system in its cellular environment: the Golgi apparatus. This project will provide a comprehensive understanding of the polymerisation of GAG chains at all biological scales, from molecules to cells, laying the foundations for future research on the function of GAGs in health and disease.