title: J proteins catalytically activate Hsp70 molecules to trap a wide range of peptide sequences.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: B
authors.initials: B
authors.lastname: Misselwitz
authors.forename: O
authors.initials: O
authors.lastname: Staeck
authors.forename: T A
authors.initials: TA
authors.lastname: Rapoport
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000302:isolation & purification / Q000378:metabolism*; D006360:Heat-Shock Proteins; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008954:Models, Biological; D009711:Nucleotides / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism*; D011487:Protein Conformation; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance
chemical_list: D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C060153:KAR2 protein, yeast; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009711:Nucleotides; D010455:Peptides; C074215:SEC63 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases