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

Berry, Richard, Headey, Stephen J., Call, Melissa J., McCluskey, James, Tregaskes, Clive A., Kaufman, Jim, Koh, Ruide, Scanlon, Martin J., Call, Matthew E. and Rossjohn, Jamie 2014. Structure of the chicken CD3εδ/γ heterodimer and its assembly with the αβT cell receptor. The Journal of Biological Chemistry 289 (12) , pp. 8240-8251. 10.1074/jbc.M113.544965

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In mammals, the αβT cell receptor (TCR) signaling complex is composed of a TCRαβ heterodimer that is non-covalently 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, non-conserved 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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Cell signaling; Immunology; Protein assembly; Protein evolution; Protein structure
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 1083-351X
Date of Acceptance: 31 January 2014
Last Modified: 04 Jun 2017 09:07

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