Madhurima, K and Nandi, B and Munshi, S and Naganathan, AN and Nandi, A (2023) Functional regulation of an intrinsically disordered protein via a conformationally excited state. In: Science advances, 9 (26). eadh4591.
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Abstract
A longstanding goal in the field of intrinsically disordered proteins (IDPs) is to characterize their structural heterogeneity and pinpoint the role of this heterogeneity in IDP function. Here, we use multinuclear chemical exchange saturation (CEST) nuclear magnetic resonance to determine the structure of a thermally accessible globally folded excited state in equilibrium with the intrinsically disordered native ensemble of a bacterial transcriptional regulator CytR. We further provide evidence from double resonance CEST experiments that the excited state, which structurally resembles the DNA-bound form of cytidine repressor (CytR), recognizes DNA by means of a "folding-before-binding" conformational selection pathway. The disorder-to-order regulatory switch in DNA recognition by natively disordered CytR therefore operates through a dynamical variant of the lock-and-key mechanism where the structurally complementary conformation is transiently accessed via thermal fluctuations.
| Item Type: | Journal Article |
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| Publication: | Science advances |
| Publisher: | NLM (Medline) |
| Additional Information: | The copyright for this article belongs to the Author. |
| Keywords: | DNA; intrinsically disordered protein; protein binding, chemistry; nuclear magnetic resonance spectroscopy; protein conformation; protein folding, DNA; Intrinsically Disordered Proteins; Magnetic Resonance Spectroscopy; Protein Binding; Protein Conformation; Protein Folding |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 28 Jul 2023 08:54 |
| Last Modified: | 28 Jul 2023 08:54 |
| URI: | https://eprints.iisc.ac.in/id/eprint/82578 |
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