N. Brot et al., SIMILARITY OF NUCLEOTIDE INTERACTIONS OF BIP AND GTP-BINDING PROTEINS, Proceedings of the National Academy of Sciences of the United Statesof America, 91(25), 1994, pp. 12120-12124
BiP is a member of the Hsp70 heat shock protein family found in the lu
men of the endoplasmic reticulum, that binds to a variety of proteins
destined to be secreted. Substance P (SP) has been used as a model pep
tide to study the interaction of BiP with protein substrates. SP stimu
lates BiP ATPase activity and forms a stable complex with BiP that is
dissociated in the presence of levels of ATP > 50 mu M. At lower conce
ntrations of ATP, the SP remains bound to BiP, and the results are con
sistent with tbe view that a BiP-ATP complex is initially formed that
reacts with SP to form a ternary complex, SP-BiP-ATP. Hydrolysis of AT
P in this complex yields a SP-BiP-ADP complex. An exchange of ATP with
ADP bound to BiP has also been demonstrated, and the results suggest
that the interactions of BiP with ATP resemble those seen with GTP-bin
ding proteins and GTP.