4Y8A

Crystal Structure of the N-terminal domain of CEACAM6

4Y8A の概要

• エントリーDOI: 10.2210/pdb4y8a/pdb
• 関連するPDBエントリー: 4Y88 4Y89 4Y8B
• 分子名称: Carcinoembryonic antigen-related cell adhesion molecule 6, ZINC ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: cell adhesion
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor: P40199
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 24652.72

構造登録者

Bonsor, D.A.,Sundberg, E.J. (登録日: 2015-02-16, 公開日: 2015-10-07, 最終更新日: 2023-09-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.83 Å)