Structure of the chicken CD3εδ/γ heterodimer and its assembly with the αβT cell receptor.
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.
From the Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
Richard
R
Berry
Stephen J
SJ
Headey
Melissa J
MJ
Call
James
J
McCluskey
Clive A
CA
Tregaskes
Jim
J
Kaufman
Ruide
R
Koh
Martin J
MJ
Scanlon
Matthew E
ME
Call
Jamie
J
Rossjohn
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry*; D017252:CD3 Complex / Q000737:chemistry* / Q000378:metabolism; D002645:Chickens / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D055503:Protein Multimerization; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016415:Sequence Alignment
D030161:Avian Proteins; D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; C472562:CD3delta antigen; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta
Cell Signaling; Immunology; Protein Assembly; Protein Evolution; Protein Structure