scholarly journals Electrostatic interactions in the denatured state ensemble: Their effect upon protein folding and protein stability

2008 ◽  
Vol 469 (1) ◽  
pp. 20-28 ◽  
Author(s):  
Jae-Hyun Cho ◽  
Satoshi Sato ◽  
Jia-Cherng Horng ◽  
Burcu Anil ◽  
Daniel P. Raleigh
Keyword(s):  
Protein Folding ◽  
Protein Stability ◽  
Electrostatic Interactions ◽  
Denatured State ◽  
State Ensemble

scholarly journals Charge-charge interactions influence the denatured state ensemble and contribute to protein stability

2000 ◽  
Vol 9 (7) ◽  
pp. 1395-1398 ◽  
Author(s):  
C. Nick Pace ◽  
Roy W. Alston ◽  
Kevin L. Shaw
Keyword(s):  
Protein Stability ◽  
Denatured State ◽  
State Ensemble ◽  
Charge Interactions

scholarly journals Protein folding by distributed computing and the denatured state ensemble

2005 ◽  
Vol 102 (46) ◽  
pp. 16684-16689 ◽  
Author(s):  
N. J. Marianayagam ◽  
N. L. Fawzi ◽  
T. Head-Gordon
Keyword(s):  
Protein Folding ◽  
Distributed Computing ◽  
Denatured State ◽  
State Ensemble

scholarly journals Differential strengths of molecular determinants guide environment specific mutational fates

2017 ◽  
Author(s):  
Rohan Dandage ◽  
Rajesh Pandey ◽  
Gopal Jayaraj ◽  
Kausik Chakraborty
Keyword(s):  
Protein Folding ◽  
Molecular Evolution ◽  
Protein Stability ◽  
Environmental Effects ◽  
Environmental Conditions ◽  
Fitness Landscape ◽  
Dependent Manner ◽  
The Common ◽  
Physical And Chemical ◽  
Substrate Binding Protein

AbstractUnder the influence of selection pressures imposed by natural environments, organisms maintain competitive fitness through underlying molecular evolution of individual genes across the genome. For molecular evolution, how multiple interdependent molecular constraints play a role in determination of fitness under different environmental conditions is largely unknown. Here, using Deep Mutational Scanning (DMS), we quantitated empirical fitness of ∼2000 single site mutants of Gentamicin-resistant gene (GmR). This enabled a systematic investigation of effects of different physical and chemical environments on the fitness landscape of the gene. Molecular constraints of the fitness landscapes seem to bear differential strengths in an environment dependent manner. Among them, conformity of the identified directionalities of the environmental selection pressures with known effects of the environments on protein folding proves that along with substrate binding, protein stability is the common strong constraint of the fitness landscape. Our study thus provides mechanistic insights into the molecular constraints that allow accessibility of mutational fates in environment dependent manner.Author SummaryEnvironmental conditions play a central role in both organismal adaptations and underlying molecular evolution. Understanding of environmental effects on evolution of genotype is still lacking a depth of mechanistic insights needed to assist much needed ability to forecast mutational fates. Here, we address this issue by culminating high throughput mutational scanning using deep sequencing. This approach allowed comprehensive mechanistic investigation of environmental effects on molecular evolution. We monitored effects of various physical and chemical environments onto single site mutants of model antibiotic resistant gene. Alongside, to get mechanistic understanding, we identified multiple molecular constraints which contribute to various degrees in determining the resulting survivabilities of mutants. Across all tested environments, we find that along with substrate binding, protein stability stands out as the common strong constraints. Remarkable direct dependence of the environmental fitness effects on the type of environmental alteration of protein folding further proves that protein stability is the major constraint of the gene. So, our findings reveal that under the influence of environmental conditions, mutational fates are channeled by various degrees of strengths of underlying molecular constraints.

scholarly journals Lipid bilayer induces contraction of the denatured state ensemble of a helical-bundle membrane protein

2021 ◽  
Vol 119 (1) ◽  
pp. e2109169119
Author(s):  
Kristen A. Gaffney ◽  
Ruiqiong Guo ◽  
Michael D. Bridges ◽  
Shaima Muhammednazaar ◽  
Daoyang Chen ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Limited Proteolysis ◽  
Water Soluble ◽  
Disordered Proteins ◽  
Resonance Spectroscopy ◽  
Denatured State ◽  
E Coli ◽  
State Ensemble

Defining the denatured state ensemble (DSE) and disordered proteins is essential to understanding folding, chaperone action, degradation, and translocation. As compared with water-soluble proteins, the DSE of membrane proteins is much less characterized. Here, we measure the DSE of the helical membrane protein GlpG of Escherichia coli (E. coli) in native-like lipid bilayers. The DSE was obtained using our steric trapping method, which couples denaturation of doubly biotinylated GlpG to binding of two streptavidin molecules. The helices and loops are probed using limited proteolysis and mass spectrometry, while the dimensions are determined using our paramagnetic biotin derivative and double electron–electron resonance spectroscopy. These data, along with our Upside simulations, identify the DSE as being highly dynamic, involving the topology changes and unfolding of some of the transmembrane (TM) helices. The DSE is expanded relative to the native state but only to 15 to 75% of the fully expanded condition. The degree of expansion depends on the local protein packing and the lipid composition. E. coli’s lipid bilayer promotes the association of TM helices in the DSE and, probably in general, facilitates interhelical interactions. This tendency may be the outcome of a general lipophobic effect of proteins within the cell membranes.

scholarly journals Folding initiation sites and protein folding.

1999 ◽  
Vol 46 (3) ◽  
pp. 487-508 ◽  
Author(s):  
M Dadlez
Keyword(s):  
Protein Folding ◽  
Protein Fragments ◽  
Denatured State ◽  
Local Structures ◽  
Rate Limiting Step ◽  
Structural Preferences ◽  
Low Levels ◽  
Rate Limiting ◽  
Transition State Barrier

The paper discusses the role of local structural preferences of protein segments in the folding of proteins. First a short overview of the local, secondary structures detected in peptides, protein fragments, denatured proteins and early folding intermediates is given. Next the discussion of their role in protein folding is presented based on recent literature and data obtained in our laboratory. In conclusion it is pointed out that, during folding, local structures populated at low levels in denatured state may facilitate the crossing of the folding transition state barrier, and consequently accelerate the rate limiting step in folding. However, the data show that this effect does not follow simple rules.

Globular–disorder transition in proteins: a compromise between hydrophobic and electrostatic interactions?

2016 ◽  
Vol 18 (33) ◽  
pp. 23207-23214 ◽  
Author(s):  
Anupaul Baruah ◽  
Parbati Biswas
Keyword(s):  
Protein Folding ◽  
Electrostatic Interactions ◽  
Protein Disorder ◽  
Disorder Transition ◽  
P Protein

Protein disorder, like protein folding, satisfies the principle of minimal frustration.

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