Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/1627
Title: Intermolecular Charge-Transfer Modulates Liquid-Liquid Phase Separation and Liquid-to-Solid Maturation of an Intrinsically Disordered pH-Responsive Domain
Authors: Dogra, P.
Joshi, Ashish
Majumdar, A.
Mukhopadhyay, S.
Keywords: Charge transfer
Peptides and proteins
Liquids
Fluorescence
Issue Date: 2019
Publisher: ACS Publications
Citation: Journal of the American Chemical Society,141(51), pp. 20380-20389.
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.
URI: https://pubs.acs.org/doi/abs/10.1021/jacs.9b10892
http://hdl.handle.net/123456789/1627
Appears in Collections:Research Articles

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