The interactions of molecular chaperones with client proteins: why are they so weak?
| Autor: | Cory M. Nadel, Jason E. Gestwicki, Arielle Shkedi, Taylor Arhar |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Protein Folding
Biochemistry & Molecular Biology nuclear magnetic resonance (NMR) Protein Conformation PPI protein–protein interaction 1.1 Normal biological development and functioning PPD peptidyl-prolyl-cis/trans isomerase domain JDP J-domain protein protein–protein interactions Computational biology Protein aggregation Hsp27 heat shock protein 27 Medical and Health Sciences Biochemistry protein aggregation Protein–protein interaction Underpinning research protein folding TF trigger factor Humans chaperone Directionality RNC ribosome-nascent-chain NBD nucleotide-binding domain NMR nuclear magnetic resonance Molecular Biology biology Trigger factor Chemistry JBC Reviews RBD ribosome-binding domain Cell Biology Biological Sciences Folding (chemistry) nuclear magnetic resonance protein–protein interactions (PPIs) Cyclic nucleotide-binding domain SBD substrate-binding domain Chaperone (protein) Chemical Sciences biology.protein Protein folding PTM posttranslational modification Generic health relevance sHsp small heat shock protein Molecular Chaperones Protein Binding |
| Zdroj: | The Journal of biological chemistry, vol 297, iss 5 The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| Popis: | The major classes of molecular chaperones have highly variable sequences, sizes, and shapes, yet they all bind to unfolded proteins, limit their aggregation, and assist in their folding. Despite the central importance of this process to protein homeostasis, it has not been clear exactly how chaperones guide this process or whether the diverse families of chaperones use similar mechanisms. For the first time, recent advances in NMR spectroscopy have enabled detailed studies of how unfolded, "client" proteins interact with both ATP-dependent and ATP-independent classes of chaperones. Here, we review examples from four distinct chaperones, Spy, Trigger Factor, DnaK, and HscA-HscB, highlighting the similarities and differences between their mechanisms. One striking similarity is that the chaperones all bind weakly to their clients, such that the chaperone-client interactions are readily outcompeted by stronger, intra- and intermolecular contacts in the folded state. Thus, the relatively weak affinity of these interactions seems to provide directionality to the folding process. However, there are also key differences, especially in the details of how the chaperones release clients and how ATP cycling impacts that process. For example, Spy releases clients in a largely folded state, while clients seem to be unfolded upon release from Trigger Factor or DnaK. Together, these studies are beginning to uncover the similarities and differences in how chaperones use weak interactions to guide protein folding. |
| Databáze: | OpenAIRE |
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