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Graded structural polymorphism in a bacterial thermosensor Protein
Abhishek Narayan,
Published in American Chemical Society
2017
PMID: 27991780
Volume: 139
   
Issue: 2
Pages: 792 - 802
Abstract
Thermosensing is critical for the expression of the expression of virulence genes in pathogenic bacteria that infect warm-blooded hosts. Proteins of the Hha-family, conserved among enterobacteriaceae, have been implicated in dynamically regulating the expression of a large number of genes upon temperature shifts. However, there is little mechanistic evidence at the molecular level as to how changes in temperature are transduced into structural changes and hence the functional outcome. In this study, we delineate the conformational behavior of Cnu, a putative molecular thermosensor, employing diverse spectroscopic, calorimetric and hydrodynamic measurements. We find that Cnu displays probe-dependent unfolding in equilibrium, graded increase in structural fluctuations and temperature-dependent swelling of the dimensions of its native ensemble within the physiological range of temperatures, features that are indicative of a highly malleable native ensemble. Site-specific fluorescence and NMR experiments in combination with multiple computational approaches-statistical mechanical model, coarse-grained and all-atom MD simulations-reveal that the fourth helix of Cnu acts as a unique thermosensing module displaying varying degrees of order and orientation in response to temperature modulations while undergoing a continuous unfolding transition. Our combined experimental-computational study unravels the folding-functional landscape of a natural thermosensor protein, the molecular origins of its unfolding complexity, highlights the role of functional constraints in determining folding-mechanistic behaviors, and the design principles orchestrating the signal transduction roles of the Hha protein family. © 2016 American Chemical Society.
About the journal
JournalData powered by TypesetJournal of the American Chemical Society
PublisherData powered by TypesetAmerican Chemical Society
ISSN00027863
Open AccessNo
Concepts (53)
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    Bacteria
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    Gene expression
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    Nuclear magnetic resonance spectroscopy
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    Proteins
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    Signal transduction
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    Computational approach
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    CONFORMATIONAL BEHAVIOR
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    Functional constraints
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    HYDRODYNAMIC MEASUREMENTS
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    Structural fluctuations
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    STRUCTURAL POLYMORPHISMS
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    Temperature dependent
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    TEMPERATURE MODULATION
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    Gene expression regulation
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    Aromatic amino acid
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    Phenylalanine
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    Tryptophan
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    Tyrosine
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    Bacterial protein
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    Dna binding protein
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    Escherichia coli protein
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    HHA PROTEIN, E COLI
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    Anisotropy
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    Article
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    Calorimetry
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    Circular dichroism
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    Conformational transition
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    Controlled study
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    Differential scanning calorimetry
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    Enthalpy
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    Entropy
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    Fluorescence
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    Fluorescence spectroscopy
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    Hydrodynamics
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    NITROGEN NUCLEAR MAGNETIC RESONANCE
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    Nonhuman
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    Protein conformation
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    Protein polymorphism
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    Proton nuclear magnetic resonance
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    Quantum yield
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    Steady state
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    Temperature dependence
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    TEMPERATURE SENSE
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    Thermodynamics
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    THERMORECEPTOR
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    Ultracentrifugation
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    Biological model
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    Chemistry
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    Temperature
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    Bacterial proteins
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    Dna-binding proteins
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    Escherichia coli proteins
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    Models, biological