Structure of the chicken CD3εδ/γ heterodimer and its assembly with the αβT cell receptor

J Biol Chem. 2014 Mar 21;289(12):8240-51. doi: 10.1074/jbc.M113.544965. Epub 2014 Jan 31.


In mammals, the αβT cell receptor (TCR) signaling complex is composed of a TCRαβ heterodimer that is noncovalently coupled to three dimeric signaling molecules, CD3εδ, CD3εγ, and CD3ζζ. The nature of the TCR signaling complex and subunit arrangement in different species remains unclear however. Here we present a structural and biochemical analysis of the more primitive ancestral form of the TCR signaling complex found in chickens. In contrast to mammals, chickens do not express separate CD3δ and CD3γ chains but instead encode a single hybrid chain, termed CD3δ/γ, that is capable of pairing with CD3ε. The NMR structure of the chicken CD3εδ/γ heterodimer revealed a unique dimer interface that results in a heterodimer with considerable deviation from the distinct side-by-side architecture found in human and murine CD3εδ and CD3εγ. The chicken CD3εδ/γ heterodimer also contains a unique molecular surface, with the vast majority of surface-exposed, nonconserved residues being clustered to a single face of the heterodimer. Using an in vitro biochemical assay, we demonstrate that CD3εδ/γ can assemble with both chicken TCRα and TCRβ via conserved polar transmembrane sites. Moreover, analogous to the human TCR signaling complex, the presence of two copies of CD3εδ/γ is required for ζζ assembly. These data provide insight into the evolution of this critical receptor signaling apparatus.

Keywords: Cell Signaling; Immunology; Protein Assembly; Protein Evolution; Protein Structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Avian Proteins / chemistry*
  • CD3 Complex / chemistry*
  • CD3 Complex / metabolism
  • Chickens / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Multimerization
  • Receptor-CD3 Complex, Antigen, T-Cell / chemistry*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Sequence Alignment


  • Avian Proteins
  • CD3 Complex
  • CD3 antigen, gamma chain
  • CD3delta antigen
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta

Associated data

  • PDB/2MIM