High resolution protein‐DNA binding energy landscapes via a novel high throughput method

Plum, Georg; Breslauer, David N.; Breslauer, Kenneth J.

doi:10.1002/bip.20723

Cited by 1 publication

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“…As part of our ongoing studies into the thermodynamics of biologically relevant DNA structures, − we demonstrate here, for the first time, a new calorimetric protocol for directly measuring heat capacity differences between two ordered DNA states; namely repeat DNA bulge loop structures, considered critical intermediates in repeat DNA expansion events, and conventional duplex DNA. Importantly, we demonstrate directly measurable differences in the heat capacities in the temperature range between 0 and 50 °C without the need for error prone extrapolations between pre- and post-transition baselines, in a temperature domain not commonly accessible to direct measurements of heat capacity changes by DSC.…”

Section: Introductionmentioning

confidence: 99%

Heat Capacity Changes (ΔC_p) for Interconversions between Differentially-Ordered DNA States within Physiological Temperature Domains: Implications for Biological Regulatory Switches

Völker

Plum²,

Breslauer

2020

J. Phys. Chem. B

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Knowledge of differences in heat capacity changes (ΔC p ) between biopolymer states provides essential information about the temperature dependence of the thermodynamic properties of these states, while also revealing insights into the nature of the forces that drive the formation of functional and dysfunctional biopolymer "order." In contrast to proteins, for nucleic acids there is a dearth of direct experimental determination of this information-rich parameter, a deficiency that compromises interpretations of the ever-increasing thermodynamic analyses of nucleic acid properties; particularly as they relate to differential nucleic acid (meta)stability states and their potential biological functions. Here we demonstrate that such heat capacity differences, in fact, exist not only between traditionally measured native to fully unfolded (assumed "random coil") DNA states, but also between competing order-to-order transformations. We illustrate the experimental approach by measuring the heat capacity change between "native"/ordered, sequence homologous, "isomeric" DNA states that differ in conformation but not sequence. Importantly, these heat capacity differences occur within biologically relevant temperature ranges. In short, we describe a new and general method to measure the value of such heat capacity differences anywhere in experimentally accessible conformational and temperature space; in this case, between two metastable bulge loop states, implicated in DNA expansion diseases, and their competing, fully paired, thermodynamically more stable duplex states. This measurement reveals a ΔC p of 61 ± 7 cal mol bp −1 K −1 . Such heat capacity differences between competing DNA "native" ensemble states must be considered when evaluating equilibria between different DNA "ordered" conformations, including the assessment of the differential stabilizing forces and potential biological functions of competing DNA "structured" motifs.

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Section: Introductionmentioning

confidence: 99%

Heat Capacity Changes (ΔC_p) for Interconversions between Differentially-Ordered DNA States within Physiological Temperature Domains: Implications for Biological Regulatory Switches

Völker

Plum²,

Breslauer

2020

J. Phys. Chem. B

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High resolution protein‐DNA binding energy landscapes via a novel high throughput method

Cited by 1 publication

References 6 publications

Heat Capacity Changes (ΔC_p) for Interconversions between Differentially-Ordered DNA States within Physiological Temperature Domains: Implications for Biological Regulatory Switches

Heat Capacity Changes (ΔC_p) for Interconversions between Differentially-Ordered DNA States within Physiological Temperature Domains: Implications for Biological Regulatory Switches

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High resolution protein‐DNA binding energy landscapes via a novel high throughput method

Cited by 1 publication

References 6 publications

Heat Capacity Changes (ΔCp) for Interconversions between Differentially-Ordered DNA States within Physiological Temperature Domains: Implications for Biological Regulatory Switches

Heat Capacity Changes (ΔCp) for Interconversions between Differentially-Ordered DNA States within Physiological Temperature Domains: Implications for Biological Regulatory Switches

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Heat Capacity Changes (ΔC_p) for Interconversions between Differentially-Ordered DNA States within Physiological Temperature Domains: Implications for Biological Regulatory Switches

Heat Capacity Changes (ΔC_p) for Interconversions between Differentially-Ordered DNA States within Physiological Temperature Domains: Implications for Biological Regulatory Switches