Appenzeller-Herzog C Nyfeler B Burkhard P Santamaria I Lopez-Otin C Hauri HP 2005 Some secretory proteins leave the endoplasmic reticulum (ER) by a receptor-mediated cargo capture mechanism, but the signals required for the cargo-receptor interaction are largely unknown. Here, we describe a novel targeting motif that is composed of a high-mannose type oligosaccharide intimately associated with a surface-exposed peptide beta-hairpin loop. The motif accounts for lectin ERGIC-53-assisted ER-export of the lyososomal enzyme procathepsin Z. The second oligosaccharide chain of procathepsin Z exhibits no binding activity for ERGIC-53, illustrating the selective lectin properties of ERGIC-53. Our data suggest that the conformation-based motif is only present in fully folded procathepsin Z and that its recognition by ERGIC-53 reflects a quality control mechanism that acts complementary to the primary folding machinery in the ER. A similar oligosaccharide/beta-hairpin loop structure is present in cathepsin C, another cargo of ERGIC-53, suggesting the general nature of this ER-exit signal. To our knowledge this is the first documentation of an ER-exit signal in soluble cargo in conjunction with its decoding by a transport receptor. application/pdf https://sonar.ch/global/documents/2832 eng info:eu-repo/semantics/altIdentifier/doi/10.1091/mbc.e04-08-0708 info:eu-repo/semantics/altIdentifier/pmid/15635097 info:eu-repo/semantics/openAccess Molecular biology of the cell. - 2005 Amino Acid Motifs Amino Acid Sequence Animals Biological Transport CHO Cells Carbohydrates Carrier Proteins Cathepsin C Cathepsin K Cathepsins Cricetinae Cross-Linking Reagents DNA DNA, Complementary Electrophoresis, Polyacrylamide Gel Endoplasmic Reticulum Glycoproteins Glycoside Hydrolases Humans Immunoprecipitation Lectins Mannose-Binding Lectins Membrane Proteins Mice Models, Molecular Molecular Conformation Molecular Sequence Data Mutation Oligosaccharides Polysaccharides Protein Conformation Protein Folding Protein Sorting Signals Protein Structure, Secondary Sequence Homology, Amino Acid Transfection Carbohydrate- and conformation-dependent cargo capture for ER-exit. http://purl.org/coar/resource_type/c_6501