Tunable order-disorder continuum in protein-DNA interactions

Munshi, Sneha and Gopi, Soundhararajan and Asampille, Gitanjali and Subramanian, Sandhyaa and Campos, Luis A and Atreya, Hanudatta S and Naganathan, Athi N (2018) Tunable order-disorder continuum in protein-DNA interactions. In: NUCLEIC ACIDS RESEARCH, 46 (17). pp. 8700-8709.

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Abstract

DNA-binding protein domains (DBDs) sample diverse conformations in equilibrium facilitating the search and recognition of specific sites on DNA over millions of energetically degenerate competing sites. We hypothesize that DBDs have co-evolved to sense and exploit the strong electric potential from the array of negatively charged phosphate groups on DNA. We test our hypothesis by employing the intrinsically disordered DBD of cytidine repressor (CytR) as a model system. CytR displays a graded increase in structure, stability and folding rate on increasing the osmolarity of the solution that mimics the non-specific screening by DNA phosphates. Electrostatic calculations and an Ising-like statistical mechanical model predict that CytR exhibits features of an electric potential sensor modulating its dimensions and landscape in a unique distance-dependent manner, while DNA plays the role of a non-specific macromolecular chaperone. Accordingly, CytR binds its natural half-site faster than the diffusion-controlled limit and even random DNA conforming to an electrostatic-steering binding mechanism. Our work unravels for the first time the synergistic features of a natural electrostatic potential sensor, a novel binding mechanism driven by electrostatic frustration and disorder, and the role of DNA in promoting distance-dependent protein structural transitions critical for switching between specific and non-specific DNA-binding modes.

Item Type:	Journal Article
Publication:	NUCLEIC ACIDS RESEARCH
Publisher:	OXFORD UNIV PRESS
Additional Information:	Copyright of this article belongs to OXFORD UNIV PRESS
Department/Centre:	Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility)
Date Deposited:	23 Dec 2018 06:48
Last Modified:	23 Dec 2018 06:48
URI:	http://eprints.iisc.ac.in/id/eprint/61255

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