Identification and functional characterization of the zeta-chain dimerization motif for TCR surface expression.
We recognized a common dimerization motif between the transmembrane (TM) domain of zeta-chain family members and glycophorin A. We have shown that a glycine within the zeta-dimerization motif is critical for zeta-homodimerization and also for its association with the TCR/CD3 complex. Similarly, two residues within the CD3 delta gamma TM domains have proven to be critical for their interaction with the zeta-homodimer. A three-dimensional homology model of the zeta-chain TM domain highlights potential residues preferentially involved either in the zeta 2-CD3 or zeta 2-TCR alpha beta association, confirming our experimental findings. These results indicate that, for symmetrical reasons, the zeta-homodimer participates in the TCR/CD3 complex assembly by interacting with CD3 gamma delta TM domains, thereby masking their degradation signals located in the cytoplasmic tails.
Bolliger
L
L
Basel Institute for Immunology, Switzerland. Luca.Bolliger@roche.com
Johansson
B
B
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017124:Conserved Sequence; D019281:Dimerization; D006021:Glycophorins / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D000596:Amino Acids; D006021:Glycophorins; D008565:Membrane Proteins; D010446:Peptide Fragments; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain