J Proteins Catalytically Activate Hsp70 Molecules to Trap a Wide Range of Peptide Sequences

Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Molecular Cell (Impact Factor: 14.02). 12/1998; 2(5):593-603. DOI: 10.1016/S1097-2765(00)80158-6
Source: PubMed


Proteins of the Hsp70 family of ATPases, such as BiP, function together with J proteins to bind polypeptides in numerous cellular processes. Using a solid phase binding assay, we demonstrate that a conserved segment of the J proteins, the J domain, catalytically activates BiP molecules to bind peptides in its immediate vicinity. The J domain interacts with the ATP form of BiP and stimulates hydrolysis resulting in the rapid trapping of peptides, which are then only slowly released upon nucleotide exchange. Activation by the J domain allows BiP to trap peptides or proteins that it would not bind on its own. These results explain why BiP and probably all other Hsp70s can interact with a wide range of substrates and suggest that the J partner primarily determines the substrate specificity of Hsp70s.

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    • "Upon ATP hydrolysis, substrate association and dissociation rates decrease some 100 and 1000-fold, respectively, leading to an increase in affinity of 10 to 50-fold (Schmid et al., 1994; Mayer et al., 2000). However, ATP hydrolysis rates are very low but stimulated synergistically by the substrate itself and the J-domain cochaperone (Karzai and McMacken, 1996; Barouch et al., 1997; Misselwitz et al., 1998; Laufen et al., 1999; Silberg et al., 2004). Thus, Hsp70 acts like a mouse-trap where the substrate itself triggers its capture. "
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    11/2015; 2:58. DOI:10.3389/fmolb.2015.00058
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    • "Other stabilizing mechanisms cannot be excluded. For instance, even molecular chaperones, including GroEL, hsp70, TF, calnexin, and calrecticulin, were reported to recognize their substrates mainly through the non-hydrophobic interactions, such as electrostatic interactions and glycan-binding [79–82]. "
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