A tyrosine‐containing motif mediates ER retention of CD3‐epsilon and adopts a helix‐turn structure.

The CD3‐epsilon endoplasmic reticulum (ER) retention motif has been characterized by mutagenesis and NMR spectroscopy. Tyr177, Leu180 and Arg183 are involved in ER retention. The motif forms an elongated alpha‐helix in which the tyrosine and leucine residues are closely apposed, followed by a beta I’ turn that places Arg183 in the vicinity of Leu180. The structure formed by Tyr177 and the leucine in position +3 is reminiscent of the beta‐turn structure adopted by tyrosine‐containing endocytosis signals. Moreover, substitution of the transferrin receptor (TfR) internalization sequence by the CD3‐epsilon motif still allowed the rapid internalization of the TfR and, conversely, the chimeric protein resulting from the substitution of the CD3‐epsilon motif by the endocytosis signal of the low density lipoprotein receptor was ER located. These data support the idea of a functional homology between the two types of signal.