4YIQ

Structure of the CEACAM6-CEACAM8 heterodimer

Summary for 4YIQ

• Entry DOI: 10.2210/pdb4yiq/pdb
• Descriptor: Carcinoembryonic antigen-related cell adhesion molecule 8, Carcinoembryonic antigen-related cell adhesion molecule 6, GLYCEROL, ... (5 entities in total)
• Functional Keywords: cell adhesion
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane; Lipid-anchor, GPI-anchor: P31997 P40199
• Total number of polymer chains: 4
• Total formula weight: 48099.07

Authors

Bonsor, D.A.,Sundberg, E.J. (deposition date: 2015-03-02, release date: 2015-10-07, Last modification date: 2023-09-27)

Primary citation

Bonsor, D.A.,Gunther, S.,Beadenkopf, R.,Beckett, D.,Sundberg, E.J.
Diverse oligomeric states of CEACAM IgV domains.
Proc.Natl.Acad.Sci.USA, 112:13561-13566, 2015

PubMed 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.

PubMed: 26483485
DOI: 10.1073/pnas.1509511112

Experimental method

X-RAY DIFFRACTION (1.85 Å)