Structural analysis of human CEACAM1 oligomerization

The human (h) CEACAM1 GFCC' face serves as a binding site for homophilic and heterophilic interactions with various microbial and host ligands. hCEACAM1 has also been observed to form oligomers and micro-clusters on the cell surface which are thought to regulate hCEACAM1-mediated signaling. However, the structural basis for hCEACAM1 higher-order oligomerization is currently unknown. To understand this, we report a hCEACAM1 IgV oligomer crystal structure which shows how GFCC' face-mediated homodimerization enables highly flexible ABED face interactions to arise. Structural modeling and nuclear magnetic resonance (NMR) studies predict that such oligomerization is 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 biophysical insights on how GFCC' and ABED face interactions together with metal ion binding may facilitate hCEACAM1 oligomerization beyond dimerization. The crystal structure of human CEACAM1 IgV oligomer and structural analyses provide insight into higher-order oligomerization involving GFCC' face-mediated homodimerization, flexible ABED interfaces, and dynamic metal-ion bridging.

Automated summary

This study investigates the oligomer structure of human CEACAM1 protein and reveals that homodimerization mediated by the GFCC' face enables flexible interactions with the ABED face. Structural modeling and NMR studies suggest that carbohydrate side-chain modifications do not hinder oligomerization. Furthermore, the presence of a conserved metal ion binding site on the G strand of the FG loop enhances oligomerization. These findings provide biophysical insights into the mechanisms of CEACAM1 oligomerization beyond dimerization.