A conditional secretory mutant in an Ig L chain is caused by replacement of tyrosine/phenylalanine 87 with histidine.
The kappa-chain of the myeloma MOPC 21 is an unusual L chain, in that it is not secreted unless complexed with a H chain. This nonsecreted kappa-chain seems to be retained in the endoplasmic reticulum in association with the protein BiP/GRP78, both in myeloma cells and when expressed in COS-1 fibroblasts. By assaying the fate of the MOPC 21 kappa-chain and its mutated derivatives in COS-1 cells, we show that the cause of the nonsecreted phenotype is the presence of histidine in position 87 of the variable domain. When this amino acid is changed back to the tyrosine that usually occupies position 87, secretion of the unassembled kappa-chain is restored. As in B lymphoid cells, co-expression of gamma H chains in COS-1 cells complements the mutation in the L chain, and rescues secretion of the arrested kappa. Thus, the presence of histidine at position 87 creates a conditional L chain secretory mutant: it is not compatible with normal transport of free L chain, but can be rescued in the presence of H chain.
Dul
J L
JL
Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.
Burrone
O R
OR
Argon
Y
Y
D001483:Base Sequence; D006639:Histidine / Q000737:chemistry; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010649:Phenylalanine / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000737:chemistry
D007145:Immunoglobulin kappa-Chains; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D014443:Tyrosine; D010649:Phenylalanine; D006639:Histidine