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 ch aracterized by mutagenesis and NMR spectroscopy. Tyr177, Leu180 and Ar g183 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 Leu18 0. The structure formed by Tyr177 and the leucine in position +3 is re miniscent of the beta-turn structure adopted by tyrosine-containing en docytosis 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 pro tein resulting from the substitution of the CD3-epsilon motif by the e ndocytosis signal of the low density lipoprotein receptor was ER locat ed. These data support the idea of a functional homology between the t wo types of signal.