Related Experiment Video
Updated: Mar 31, 2026
Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
Published on: March 24, 2017
Diverse oligomeric states of CEACAM IgV domains
Daniel A Bonsor1, Sebastian Günther1, Robert Beadenkopf1
1Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201;
Abstract:
Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) comprise a large family of cell surface adhesion molecules that bind to themselves and other family members to carry out numerous cellular functions, including proliferation, signaling, differentiation, tumor suppression, and survival. They also play diverse and significant roles in immunity and infection. The formation of CEACAM oligomers is caused predominantly by interactions between their N-terminal IgV domains. Although X-ray crystal structures of CEACAM IgV domain homodimers have been described, how CEACAMs form heterodimers or remain monomers is poorly understood. To address this key aspect of CEACAM function, we determined the crystal structures of IgV domains that form a homodimeric CEACAM6 complex, monomeric CEACAM8, and a heterodimeric CEACAM6-CEACAM8 complex. To confirm and quantify these interactions in solution, we used analytical ultracentrifugation to measure the dimerization constants of CEACAM homodimers and isothermal titration calorimetry to determine the thermodynamic parameters and binding affinities of CEACAM heterodimers. We found the CEACAM6-CEACAM8 heterodimeric state to be substantially favored energetically relative to the CEACAM6 homodimer. Our data provide a molecular basis for the adoption of the diverse oligomeric states known to exist for CEACAMs and suggest ways in which CEACAM6 and CEACAM8 regulate the biological functions of one another, as well as of additional CEACAMs with which they interact, both in cis and in trans.
Insights
Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) form diverse structures. New crystal structures reveal CEACAM6-CEACAM8 heterodimers are energetically favored, explaining CEACAMs
Area of Science:
- Cellular adhesion
- Molecular biology
- Structural biology
Background:
- Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are cell surface proteins involved in proliferation, signaling, differentiation, tumor suppression, survival, immunity, and infection.
- CEACAM oligomerization, primarily through N-terminal IgV domains, dictates their function, but heterodimerization and monomeric states remain poorly understood.
Purpose of the Study:
- To elucidate the structural basis of CEACAM heterodimerization and monomerization.
- To investigate the formation of CEACAM6 homodimers, CEACAM8 monomers, and CEACAM6-CEACAM8 heterodimers.
Main Methods:
- X-ray crystallography to determine the structures of CEACAM IgV domains in various oligomeric states.
- Analytical ultracentrifugation to quantify homodimerization constants.
- Isothermal titration calorimetry to determine thermodynamic parameters and binding affinities of heterodimers.
Main Results:
- Crystal structures of CEACAM6 homodimers, CEACAM8 monomers, and CEACAM6-CEACAM8 heterodimers were determined.
- The CEACAM6-CEACAM8 heterodimeric state was found to be energetically favored over the CEACAM6 homodimer.
- Solution-based biophysical methods confirmed and quantified these interactions.
Conclusions:
- The study provides a molecular understanding of CEACAMs' diverse oligomeric states.
- Findings suggest CEACAM6 and CEACAM8 mutually regulate each other's biological functions and those of other CEACAMs.
- This work offers insights into CEACAM-mediated cellular processes in both normal and pathological conditions.
More Related Videos
12:15The C. elegans Intestine As a Model for Intercellular Lumen Morphogenesis and In Vivo Polarized Membrane Biogenesis at the Single-cell Level: Labeling by Antibody Staining, RNAi Loss-of-function Analy
Published on: October 3, 2017
08:51Identification of Mouse and Human Antibody Repertoires by Next-Generation Sequencing
Published on: March 15, 2019
Related Concept Videos
01:31Immunoglobulin-like Cell Adhesion Molecules
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
01:28Diversity of Antigen Receptors
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
01:10Antibody Structure
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
01:10Antibody Structure
01:15Transcytosis of IgG
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
01:25Structure of Cadherins