PDBsum entry 4y8a

Cell adhesion

PDB id: 4y8a

Contents

Protein chains

108 a.a.

Ligands

GOL ×4

Metals

_ZN ×7

Waters ×118

PDB id:

4y8a

Name:

Cell adhesion

Title:

Crystal structure of the n-terminal domain of ceacam6

Structure:

Carcinoembryonic antigen-related cell adhesion molecule 6. Chain: a, b. Fragment: igv domain (unp residues 34-141). Synonym: non-specific crossreacting antigen,normal cross-reacting antigen. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ceacam6, nca. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.83Å R-factor: 0.169 R-free: 0.195

Authors:

D.A.Bonsor,E.J.Sundberg

Key ref:

D.A.Bonsor et al. (2015). Diverse oligomeric states of CEACAM IgV domains. Proc Natl Acad Sci U S A, 112, 13561-13566. PubMed id: 26483485 DOI: 10.1073/pnas.1509511112

Date:

16-Feb-15 Release date: 07-Oct-15

Protein chains

P40199  (CEAM6_HUMAN) -  Carcinoembryonic antigen-related cell adhesion molecule 6 from Homo sapiens

Seq: 344 a.a.

Struc: 108 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1073/pnas.1509511112

Proc Natl Acad Sci U S A 112:13561-13566 (2015)

PubMed id: 26483485

Diverse oligomeric states of CEACAM IgV domains.

D.A.Bonsor, S.Günther, R.Beadenkopf, D.Beckett, E.J.Sundberg.

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.