GRP94 (glucose-regulated protein of 94 kDa) is a major luminal constituent of the endoplasmic reticulum with known high capacity for calcium in vivo and a peptide-binding activity in vitro. In the present study, we show that Ca²⁺ regulates the ability of GRP94 to bind peptides. This effect is due to a Ca²⁺-binding site located in the charged linker domain of GRP94, which, when occupied, enhances the association of peptides with the peptide-binding site in the N-terminal domain of the protein. We further show that grp94^?/? cells are hypersensitive to perturbation of intracellular calcium and thus GRP94 is important for cellular Ca²⁺ storage.

calcium store, chaperone, endoplasmic reticulum (ER), glucose-regulated protein of 94 kDa (GRP94), heat-shock protein (hsp)