The peptide-binding activity of GRP94 is regulated by calcium.
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.
Biswas
Chhanda
C
Division of Cell Pathology, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA.
Ostrovsky
Olga
O
Makarewich
Catherine A
CA
Wanderling
Sherry
S
Gidalevitz
Tali
T
Argon
Yair
Y
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000378:metabolism*; D018411:Spodoptera
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D010455:Peptides; C053387:endoplasmin; D002118:Calcium