A molecular specificity code for the three mammalian KDEL receptors.
AC-terminal KDEL-like motif prevents secretion of soluble endoplasmic reticulum (ER)-resident proteins. This motif interacts with KDEL receptors localized in the intermediate compartment and Golgi apparatus. Such binding triggers retrieval back to the ER via a coat protein I-dependent pathway. To date, two human KDEL receptors have been reported. Here, we report the Golgi localization of a third human KDEL receptor. Using a reporter construct system from a screen of 152 variants, we identified 35 KDEL-like variants that result in efficient ER localization but do not match the current Prosite motif for ER localization ([KRHQSA]-[DENQ]-E-L). We cloned 16 human proteins with one of these motifs and all were found in the ER. A subsequent screen by bimolecular fluorescence complementation determined the specificities of the three human KDEL receptors. Each KDEL receptor has a unique pattern of motifs with which it interacts. This suggests a specificity in the retrieval of human proteins that contain different KDEL variants.
Raykhel
Irina
I
Department of Biochemistry, Biocenter Oulu, University of Oulu, 90570 Oulu, Finland.
Alanen
Heli
H
Salo
Kirsi
K
Jurvansuu
Jaana
J
Nguyen
Van Dat
VD
Latva-Ranta
Maria
M
Ruddock
Lloyd
L
D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017930:Genes, Reporter; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals; D018000:Receptors, Peptide / Q000032:analysis / Q000737:chemistry*; D016415:Sequence Alignment
C064459:KDEL receptor; D021382:Protein Sorting Signals; D018000:Receptors, Peptide