Abstract
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 sequences1,2, soon after their translocation into the endoplasmic reticulum3,4. GRP94, another endoplasmic reticulum stress protein5,6 homologous to HSP907–11, also associates with unassembled immunoglobulin chains12, 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.
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Melnick, J., Dul, J. & Argon, Y. Sequential interaction of the chaperones BiP and GRP94 with immunoglobulin chains in the endoplasmic reticulum. Nature 370, 373–375 (1994). https://doi.org/10.1038/370373a0
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DOI: https://doi.org/10.1038/370373a0
