CONICET | Buscador de Institutos y Recursos Humanos

Antibodies or immunoglobulins are key components of the immune system. These glycoproteins are central to the humoral adaptive immune response: they act by binding to pathogens and toxins, and this process could allow their direct neutralization, or trigger the involvement of the complement system and/or phagocytic cells in order to eliminate the threat. In particular, secretory IgA (sIgA) is the major immunoglobulin at mucosal sites, a glycoprotein consisting of a secretory component covalently attached to dimeric IgA with one joining (J) chain. Immunoglobulin A (IgA) plays an important role in maintaining a balance with the commensal bacterial flora, in protecting our mucosal surfaces, and in extending maternal immunity via breast feeding. sIgA contains several sites of glycosylation and alterations in their structure caninterfere with its immune function in the gut. It is worth noting that IgA is heavily glycosylated, and the presence of these N- and/or O-glycans (depending on the subtype) may result of importance in mantaining the protein conformation.The main purpose of this work is to evaluate the impact of glycosylation in the structure of monomeric IgA, and how structural changes induced by its glycans may possibly affect IgA physiological function, by means of classical molecular dynamics simulations. We started by identifying glycosylation sites in the Fab (antigen-binding fragment) of IgA, as provided by the structures deposited in the Protein Data Base (PDBid 5E8E). We then proceeded to simulate two simplified systems, corresponding to a region of the Fab in the presence or absence of N-glycosylation. With the use of computational tools, we analyzed how the presence of certain carbohydrates modulates the conformation of the Fab. Possible consequences of the role of glycosylation in the protein function are discussed.