Structural biology-based approaches in understanding CEACAM1 oligomerization and binding with microbial ligands

Human (h) carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) mediates homophilic and heterophilic interactions with various microbial and host ligands and is a very important immunoreceptor important in mediating immune T cell tolerance. To understand hCEACAM1 mediated interactions, we decipher hCEACAM1 structural approached to predict how GFCC’ face regulates homodimerization and heterophilic associations. In addition, associations through’ face enables highly flexible ABED face interactions to arise. Structural modeling and predict that such oligomerization and microbial binds are not impeded by the presence of carbohydrate side- chain modifications. In addition, using UV spectroscopy and NMR studies, we show that oligomerization is further facilitated by the presence of a conserved metal ion (Zn++ or Ni++) binding site on the G strand of the FG loop. Together these studies provide therapeutical insights on how GFCC’ and ABED face interactions together with metal ion binding may facilitate hCEACAM1 oligomerization beyond dimerization and facilitate microbial and host ligands binding.