7RPP

Crystal structure of human CEACAM1 with GFCC' and ABED face

7RPP の概要

• エントリーDOI: 10.2210/pdb7rpp/pdb
• 分子名称: Carcinoembryonic antigen-related cell adhesion molecule 1, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: ceacam1, immune system
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 35821.65

構造登録者

Gandhi, A.K.,Kim, W.M.,Sun, Z.-Y.,Huang, Y.H.,Petsko, G.A.,Blumberg, R.S. (登録日: 2021-08-04, 公開日: 2022-08-10, 最終更新日: 2023-10-18)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)