J-PROTEINS CATALYTICALLY ACTIVATE HSP70 MOLECULES TO TRAP A WIDE-RANGE OF PEPTIDE SEQUENCES

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.