B. Misselwitz et al., J-PROTEINS CATALYTICALLY ACTIVATE HSP70 MOLECULES TO TRAP A WIDE-RANGE OF PEPTIDE SEQUENCES, MOLECULAR CELL, 2(5), 1998, pp. 593-603
Proteins of the Hsp70 family of ATPases, such as BiP, function togethe
r with J proteins to bind polypeptides in numerous cellular processes.
Using a solid phase binding assay, we demonstrate that a conserved se
gment of the J proteins, the J domain, catalytically activates BiP mol
ecules to bind peptides in its immediate vicinity. The J domain intera
cts with the ATP form of BiP and stimulates hydrolysis resulting in th
e rapid trapping of peptides, which are then only slowly released upon
nucleotide exchange. Activation by the J domain allows BiP to trap pe
ptides or proteins that it would not bind on its own. These results ex
plain why BiP and probably all other Hsp70s can interact with a wide r
ange of substrates and suggest that the J partner primarily determines
the substrate specificity of Hsp70s.