Polyphosphate specifically cooperates with Hfq to silence prophages and mobile genetic elements in the bacterial chromosome.

The folding of proteins into their native structure is crucial for the functioning of all biological processes. Molecular chaperones are guardians of the proteome that assist in protein folding and prevent the accumulation of aberrant protein conformations that can lead to proteotoxicity. ATP-independent chaperones do not require ATP to regulate their functional cycle. Although these chaperones have been traditionally regarded as passive holdases that merely prevent aggregation, recent work has shown that they can directly affect the folding energy landscape by tuning their affinity to various folding states of the client. This review focuses on emerging paradigms in the mechanism of action of ATP-independent chaperones and on the various modes of regulating client binding and release.

The formation and deposition of amyloid fibrils have been linked to the pathogenesis of numerous debilitating neurodegenerative disorders. Serum albumins serve as good model proteins for understanding the molecular mechanisms of protein aggregation and fibril formation. Graphene-based nanotherapeutics appear to be promising candidates for designing inhibitors of protein fibrillation. The inhibitory effect of graphene oxide (GO) nanoparticles on the fibrillation of human serum albumin (HSA) in an in vitro mixed solvent system has been investigated. The methods used include ThT fluorescence, ANS binding, Trp fluorescence, circular dichroism, fluorescence microscopy, field-emission scanning electron microscopy, and high-resolution transmission electron microscopy. It was observed that GO inhibits HSA fibrillation and forms agglomerates with β-sheet rich prefibrillar species. Binding of GO prevents the formation of mature fibrils with characteristic cross-β sheet but does not promote refolding to the native state.

ATP-independent chaperones are usually considered to be holdases that rapidly bind to non-native states of substrate proteins and prevent their aggregation. These chaperones are thought to release their substrate proteins prior to their folding. Spy is an ATP-independent chaperone that acts as an aggregation inhibiting holdase but does so by allowing its substrate proteins to fold while they remain continuously chaperone bound, thus acting as a foldase as well. The attributes that allow such dual chaperoning behavior are unclear. Here, we used the topologically complex protein apoflavodoxin to show that the outcome of Spy’s action is substrate specific and depends on its relative affinity for different folding states. Tighter binding of Spy to partially unfolded states of apoflavodoxin limits the possibility of folding while bound, converting Spy to a holdase chaperone. Our results highlight the central role of the substrate in determining the mechanism of chaperone action.