Structure of the chicken CD3??/? heterodimer and its assembly with the ??T cell receptor.

ABSTRACT: In mammals, the ??T cell receptor (TCR) signaling complex is composed of a TCR?? heterodimer that is noncovalently coupled to three dimeric signaling molecules, CD3??, CD3??, and CD3??. 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 CD3? and CD3? chains but instead encode a single hybrid chain, termed CD3?/?, that is capable of pairing with CD3?. The NMR structure of the chicken CD3??/? 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 CD3?? and CD3??. The chicken CD3??/? 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 CD3??/? can assemble with both chicken TCR? and TCR? via conserved polar transmembrane sites. Moreover, analogous to the human TCR signaling complex, the presence of two copies of CD3??/? is required for ?? assembly. These data provide insight into the evolution of this critical receptor signaling apparatus.

SUBMITTER: Berry R 

PROVIDER: S-EPMC3961652 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature