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Differential modulation of energy landscapes of cyclic AMP receptor protein (CRP) as a regulatory mechanism for class II CRP-dependent promoters.

ABSTRACT: The Escherichia coli cAMP receptor protein, CRP, is a homodimeric global transcription activator that employs multiple mechanisms to modulate the expression of hundreds of genes. These mechanisms require different interfacial interactions among CRP, RNA, and DNA of varying sequences. The involvement of such a multiplicity of interfaces requires a tight control to ensure the desired phenotype. CRP-dependent promoters can be grouped into three classes. For decades scientists in the field have been puzzled over the differences in mechanisms between class I and II promoters. Using a new crystal structure, IR spectroscopy, and computational analysis, we defined the energy landscapes of WT and 14 mutated CRPs to determine how a homodimeric protein can distinguish nonpalindromic DNA sequences and facilitate communication between residues located in three different activation regions (AR) in CRP that are ?30 Å apart. We showed that each mutation imparts differential effects on stability among the subunits and domains in CRP. Consequently, the energetic landscapes of subunits and domains are different, and CRP is asymmetric. Hence, the same mutation can exert different effects on ARs in class I or II promoters. The effect of a mutation is transmitted through a network by long-distance communication not necessarily relying on physical contacts between adjacent residues. The mechanism is simply the sum of the consequences of modulating the synchrony of dynamic motions of residues at a distance, leading to differential effects on ARs in different subunits. The computational analysis is applicable to any system and potentially with predictive capability.

SUBMITTER: Evangelista W

PROVIDER: S-EPMC6802525 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Differential modulation of energy landscapes of cyclic AMP receptor protein (CRP) as a regulatory mechanism for class II CRP-dependent promoters.

Evangelista Wilfredo W Dong Aichun A White Mark A MA Li Jianquan J Lee J Ching JC

The Journal of biological chemistry 20190906 42

The <i>Escherichia coli</i> cAMP receptor protein, CRP, is a homodimeric global transcription activator that employs multiple mechanisms to modulate the expression of hundreds of genes. These mechanisms require different interfacial interactions among CRP, RNA, and DNA of varying sequences. The involvement of such a multiplicity of interfaces requires a tight control to ensure the desired phenotype. CRP-dependent promoters can be grouped into three classes. For decades scientists in the field ha ...[more]

PMID: 31492755

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Dataset Information

Differential modulation of energy landscapes of cyclic AMP receptor protein (CRP) as a regulatory mechanism for class II CRP-dependent promoters.

Publications

Differential modulation of energy landscapes of cyclic AMP receptor protein (CRP) as a regulatory mechanism for class II CRP-dependent promoters.

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