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

• Published in: Molecular cell Vol. 2; no. 5; pp. 593 - 603
• Main Authors: Misselwitz, Benjamin, Staeck, Oliver, Rapoport, Tom A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.1998
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Triphosphatases - metabolism; Adenosine Triphosphate - metabolism; Binding Sites; Chromatography, High Pressure Liquid; Enzyme Activation; Fungal Proteins - chemistry; Fungal Proteins - isolation & purification; Fungal Proteins - metabolism; Heat-Shock Proteins; HSP70 Heat-Shock Proteins - isolation & purification; HSP70 Heat-Shock Proteins - metabolism; Kinetics; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Membrane Transport Proteins; Models, Biological; Nucleotides - metabolism; Peptides - chemical synthesis; Peptides - metabolism; Protein Conformation; Saccharomyces cerevisiae Proteins; Substrate Specificity; Surface Plasmon Resonance
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(00)80158-6

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.