Mechanisms contributing to T cell receptor signaling and assembly revealed by the solution structure of an ectodomain fragment of the CD3 epsilon gamma heterodimer.
The T cell receptor (TCR) consists of genetically diverse disulfide-linked alpha and beta chains in noncovalent association with the invariant CD3 subunits. CD3 epsilon and CD3 gamma are integral components of both the TCR and pre-TCR. Here, we present the solution structure of a heterodimeric CD3 epsilon gamma ectodomain complex. A unique side-to-side hydrophobic interface between the two C2-set immunoglobulin-like domains and parallel pairing of their respective C-terminal beta strands are revealed. Mutational analysis confirms the importance of the distinctive linkage as well as the membrane proximal stalk motif (RxCxxCxE) for domain-domain association. These biochemical and structural analyses offer insights into the modular pairwise association of CD3 invariant chains. More importantly, the findings suggest how the rigidified CD3 elements participate in TCR-based signal transduction.
Sun
Z J
ZJ
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Kim
K S
KS
Wagner
G
G
Reinherz
E L
EL
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017252:CD3 Complex / Q000737:chemistry* / Q000378:metabolism*; D019556:COS Cells; D019281:Dimerization; D006801:Humans; D015151:Immunoblotting; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D014162:Transfection
D017252:CD3 Complex; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins