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.
Mallabiabarrena
A
A
Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Spain.
Jiménez
M A
MA
Rico
M
M
Alarcón
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017252:CD3 Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014443:Tyrosine / Q000235:genetics
D017252:CD3 Complex; D011973:Receptors, LDL; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; D014443:Tyrosine