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http://hdl.handle.net/123456789/1627
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DC Field | Value | Language |
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dc.contributor.author | Dogra, P. | - |
dc.contributor.author | Joshi, Ashish | - |
dc.contributor.author | Majumdar, A. | - |
dc.contributor.author | Mukhopadhyay, S. | - |
dc.date.accessioned | 2020-11-16T05:02:27Z | - |
dc.date.available | 2020-11-16T05:02:27Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Journal of the American Chemical Society,141(51), pp. 20380-20389. | en_US |
dc.identifier.other | 10.1021/jacs.9b10892 | - |
dc.identifier.uri | https://pubs.acs.org/doi/abs/10.1021/jacs.9b10892 | - |
dc.identifier.uri | http://hdl.handle.net/123456789/1627 | - |
dc.description.abstract | Liquid–liquid phase separation of intrinsically disordered proteins into mesoscopic, dynamic, liquid-like supramolecular condensates is thought to govern critical cellular functions. These condensates can mature from a functional liquid-like state to a pathological gel-like or solid-like state. Here, we present a unique case to demonstrate that an unusual cascade of intermolecular charge-transfer coupled with a multitude of transient noncovalent interactions and conformational fluctuations can promote liquid phase condensation of a pH-responsive, intrinsically disordered, oligopeptide repeat domain of a melanosomal protein. At neutral cytosolic pH, the repeat domain forms highly dynamic, mesoscopic, permeable, liquid-like droplets possessing rapid internal diffusion and torsional fluctuations. These liquid condensates mature via pervasive intermolecular charge-transfer and persistent backbone interactions driving the liquid-to-solid phase transition into heterogeneous solid-like aggregates that are structurally and morphologically distinct from typical amyloids formed at mildly acidic melanosomal pH. Our findings reveal the regulatory role of the repeat domain as a specific pH-sensor that critically controls the phase transition and self-assembly processes akin to prion-like low-complexity domains modulating intracellular phase separation. | en_US |
dc.language.iso | en | en_US |
dc.publisher | ACS Publications | en_US |
dc.subject | Charge transfer | en_US |
dc.subject | Peptides and proteins | en_US |
dc.subject | Liquids | en_US |
dc.subject | Fluorescence | en_US |
dc.title | Intermolecular Charge-Transfer Modulates Liquid-Liquid Phase Separation and Liquid-to-Solid Maturation of an Intrinsically Disordered pH-Responsive Domain | en_US |
dc.type | Article | en_US |
Appears in Collections: | Research Articles |
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