Sequential interaction of the chaperones BiP and GRP94 with immunoglobulin chains in the endoplasmic reticulum.
During their transit through the endoplasmic reticulum, newly synthesized light and heavy chains of immunoglobulins associate with two endoplasmic reticulum stress proteins. BiP/GRP78, a member of the HSP70 family, binds these polypeptides, presumably through promiscuously exposed hydrophobic sequences, soon after their translocation into the endoplasmic reticulum. GRP94, another endoplasmic reticulum stress protein homologous to HSP90, also associates with unassembled immunoglobulin chains, but its interaction is biochemically, kinetically and structurally distinct from BiP's. We report here that whereas BiP preferentially binds an early disulphide intermediate of light chain and dissociates within a few minutes, GRP94 exclusively binds fully oxidized molecules and dissociates with a half-time of 50 min. These results indicate that GRP94 is itself a chaperone which acts after BiP.
Melnick
J
J
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Dul
J L
JL
Argon
Y
Y
D020126:Brefeldin A; D002352:Carrier Proteins / Q000378:metabolism*; D018833:Chaperonins; D003517:Cyclopentanes / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D018832:Molecular Chaperones; D011485:Protein Binding / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D003517:Cyclopentanes; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007147:Immunoglobulin Light Chains; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011506:Proteins; C018551:glucose-regulated proteins; D020126:Brefeldin A; D018833:Chaperonins