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
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.
Available from: Matthias Mayer
- "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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ABSTRACT: Hsp70s chaperone an amazing number and variety of cellular protein folding processes. Key to their versatility is the recognition of a short degenerate sequence motif, present in practically all polypeptides, and a bidirectional allosteric intramolecular regulation mechanism linking their N-terminal nucleotide binding domain (NBD) and their C-terminal polypeptide substrate binding domain (SBD). Through this interdomain communication ATP binding to the NBD and ATP hydrolysis control the affinity of the SBD for polypeptide substrates and substrate binding to the SBD triggers ATP hydrolysis. Genetic screens for defective variants of Hsp70s and systematic analysis of available structures of the isolated domains revealed some residues involved in allosteric control. Recent elucidation of the crystal structure of the Hsp70 homolog DnaK in the ATP bound open conformation as well as numerous NMR and mutagenesis studies bring us closer to an understanding of the communication between NBD and SBD. In this review we will discuss our current view of the allosteric control mechanism of Hsp70 chaperones.
11/2015; 2:58. DOI:10.3389/fmolb.2015.00058
- "Kompleks Hsp60-Hsp10 (adaptacja własna wg ) cji aminokwasowej błędnie zwiniętej cząsteczki . Odmienne substraty wymagają w procesie rozwijania swoich łańcuchów udziału różnych białek z rodziny Hsp40 . Tymczasem domena SBD Hsp70 wykazuje mechaniczną elastyczność, umożliwiającą związanie i poddanie naprawie wielu różnorodnych białek . "
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ABSTRACT: Heat shock proteins (Hsps) are a class of proteins with highly conserved amino acid sequences. They are widespread in nature; they are found in archeons, true bacteria and eukaryotic organisms. Hsps from various families, commonly interact to execute essential cellular tasks, such as molecular regulation of newly synthesized protein-folding or restoration of the appropriate conformation of denatured and aggregated proteins. In this review we discuss mechanisms of spatial organization of protein structure mediated by Hsp10, Hsp40, Hsp60, Hsp70, Hsp104 (Hsp100) and Hsp110. Interactions between Hsps of different molecular weights are described.
Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine) 06/2014; 68:793-807. · 0.57 Impact Factor
Available from: Ahyun Son
- "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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ABSTRACT: In the processes of protein synthesis and folding, newly synthesized polypeptides are tightly connected to the macromolecules, such as ribosomes, lipid bilayers, or cotranslationally folded domains in multidomain proteins, representing a hallmark of de novo protein folding environments in vivo. Such linkage effects on the aggregation of endogenous polypeptides have been largely neglected, although all these macromolecules have been known to effectively and robustly solubilize their linked heterologous proteins in fusion or display technology. Thus, their roles in the aggregation of linked endogenous polypeptides need to be elucidated and incorporated into the mechanisms of de novo protein folding in vivo. In the classic hydrophobic interaction-based stabilizing mechanism underlying the molecular chaperone-assisted protein folding, it has been assumed that the macromolecules connected through a simple linkage without hydrophobic interactions and conformational changes would make no effect on the aggregation of their linked polypeptide chains. However, an increasing line of evidence indicates that the intrinsic properties of soluble macromolecules, especially their surface charges and excluded volume, could be important and universal factors for stabilizing their linked polypeptides against aggregation. Taken together, these macromolecules could act as folding helpers by keeping their linked nascent chains in a folding-competent state. The folding assistance provided by these macromolecules in the linkage context would give new insights into de novo protein folding inside the cell.
International Journal of Molecular Sciences 12/2012; 13(8):10368-86. DOI:10.3390/ijms130810368 · 2.86 Impact Factor
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