Comparisons of N-glycans across invertebrate phyla
The latest Paper of the Month for Parasitology is “Comparisons of N-glycans across invertebrate phyla” by Katharina Paschinger and Iain B. H. Wilson
Sugars coat the surfaces of all cells, regardless of whether they are your cells or those of a parasite – but what sort of sugars do we mean? The sugar in your coffee is a disaccharide, which means two sugar units (fructose and glucose) joined together. As each single sugar unit has up to five free reactive ‘hands’ (actually hydroxyl groups), there are many ways to join sugars together. Also, if the hands are arranged up or down, then you have chemically distinct molecules. On the cell surface, you have sugar units other than fructose and glucose: rather you find galactose, fucose and other ones which are joined together resulting in complex carbohydrate chains called glycans linked to proteins and lipids. These sugar chains can be also modified, for example, with sulphate or phosphate.
The ways the sugar units are put together varies from cell type to cell type or from species to species. Thus, your cell surfaces have a different ‘sugar coating’ as compared to those of parasites or of organisms which transmit parasites. This can be important for parasite transmission and infectivity. Therefore, it is important to compare the differences in complex sugar molecules between hosts, parasites and vectors. This is done primarily by mass spectrometry in which the ‘weight’ and the fragments of the sugar chains can be determined.
An important aspect is that a sugar chain has no biological meaning unless it is recognised by a protein. These can be antibodies from parasite-infected humans or animals, or they can be carbohydrate-binding proteins, which animals also produce as a first line of defence against infection. If you have ever had a blood test, you may find the abbreviation CRP: this stands for C-reactive protein, which is produced in response to infection or inflammation and which recognises a specific modification of bacterial and parasite sugar chains. We can determine what CRP binds in a specific organism by spotting the sugar chains onto glass slides and then incubating them with CRP, then using a fluorescent reagent to detect binding. This sort of experimental approach, known as a glycan array, is also used to find out which sugars are generating an immune response during infections of different parasitic worms.
In this review article we summarise research on the structure, biosynthesis and recognition of the so-called N-glycans (linked through nitrogen atoms on proteins) in invertebrate species, including model organisms such as the fruitfly, parasites such as schistosomes or filarial worms and mosquitoes, which are vectors for parasites. The main message: there is an incredible variety of structures, which are more than some sort of jewellery at the cell surface. By looking at differences, we can find potential Achilles’ heels of parasites or vectors. We find it exciting with each ‘new’ sample to find which unusual combinations evolution has come up with in these complex sugar chains.
Figure: Example of the analytical workflows for glycans by HPLC, mass spectrometry and array methodologies; the different type of sugar units are shown with different symbols.
Above image: Mass spectrometer, coutesy of Shutterstock
The paper “Comparisons of N-glycans across invertebrate phyla” by Katharina Paschinger and Iain B. H. Wilson is available Open access.