7RPP

Crystal structure of human CEACAM1 with GFCC' and ABED face

Summary for 7RPP

• Entry DOI: 10.2210/pdb7rpp/pdb
• Descriptor: Carcinoembryonic antigen-related cell adhesion molecule 1, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: ceacam1, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 35821.65

Authors

Gandhi, A.K.,Kim, W.M.,Sun, Z.-Y.,Huang, Y.H.,Petsko, G.A.,Blumberg, R.S. (deposition date: 2021-08-04, release date: 2022-08-10, Last modification date: 2023-10-18)

Primary citation

Gandhi, A.K.,Sun, Z.J.,Huang, Y.H.,Kim, W.M.,Yang, C.,Petsko, G.A.,Beauchemin, N.,Blumberg, R.S.
Structural analysis of human CEACAM1 oligomerization.
Commun Biol, 5:1042-1042, 2022

PubMed Abstract: 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.

PubMed: 36180783
DOI: 10.1038/s42003-022-03996-4

Experimental method

X-RAY DIFFRACTION (2.2 Å)