scholarly journals Protein unfolding mechanisms and their effects on folding experiments

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1723 ◽  
Author(s):  
Lisa J Lapidus
Keyword(s):  
Free Energy ◽  
Protein Folding ◽  
Protein Unfolding ◽  
Energy Landscape ◽  
Free Energy Landscape ◽  
Folding Kinetics ◽  
Chemical Heat ◽  
Conformational Ensembles

In this review, I discuss the various methods researchers use to unfold proteins in the lab in order to understand protein folding both in vitro and in vivo. The four main techniques, chemical-, heat-, pressure- and force-denaturation, produce distinctly different unfolded conformational ensembles. Recent measurements have revealed different folding kinetics from different unfolding mechanisms. Thus, comparing these distinct unfolded ensembles sheds light on the underlying free energy landscape of folding.

scholarly journals High-Resolution Mapping of a Repeat Protein Folding Free Energy Landscape

2016 ◽  
Vol 111 (11) ◽  
pp. 2368-2376 ◽  
Author(s):  
Martin J. Fossat ◽  
Thuy P. Dao ◽  
Kelly Jenkins ◽  
Mariano Dellarole ◽  
Yinshan Yang ◽  
...  
Keyword(s):  
Free Energy ◽  
Protein Folding ◽  
High Resolution ◽  
Energy Landscape ◽  
Free Energy Landscape ◽  
Repeat Protein ◽  
High Resolution Mapping ◽  
Resolution Mapping ◽  
Folding Free Energy

Chemical Denaturants Smoothen Ruggedness on the Free Energy Landscape of Protein Folding

Biochemistry ◽  
2017 ◽  
Vol 56 (31) ◽  
pp. 4053-4063 ◽  
Author(s):  
Pooja Malhotra ◽  
Prashant N. Jethva ◽  
Jayant B. Udgaonkar
Keyword(s):  
Free Energy ◽  
Protein Folding ◽  
Energy Landscape ◽  
Free Energy Landscape

scholarly journals Quantifying Nonnative Interactions in the Protein-Folding Free-Energy Landscape

2016 ◽  
Vol 111 (2) ◽  
pp. 287-293 ◽  
Author(s):  
Paulo Ricardo Mouro ◽  
Vinícius de Godoi Contessoto ◽  
Jorge Chahine ◽  
Ronaldo Junio de Oliveira ◽  
Vitor Barbanti Pereira Leite
Keyword(s):  
Free Energy ◽  
Protein Folding ◽  
Energy Landscape ◽  
Free Energy Landscape ◽  
Folding Free Energy

scholarly journals The Trajectory Taken by Dimeric Cu/Zn Superoxide Dismutase Through the Protein Unfolding and Dissociation Landscape Is Modulated by Salt-Bridge Formation

2019 ◽  
Author(s):  
Luke McAlary ◽  
Julian Harrison ◽  
J. Andrew Aquilina ◽  
Steven Fitzgerald ◽  
Celine Kelso ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Free Energy ◽  
Gas Phase ◽  
Protein Unfolding ◽  
Energy Landscape ◽  
Salt Bridge ◽  
Native Mass Spectrometry ◽  
Free Energy Landscape ◽  
Related Point ◽  
Macromolecular Protein

<p>Native mass spectrometry (MS) is a powerful means for studying macromolecular protein assemblies, including accessing activated states. However, much remains to be understood about what governs which regions of the protein (un)folding funnel are explored by activation of protein ions in vacuum. Here we examine the trajectory that dimeric Cu/Zn superoxide dismutase (SOD1) dimers take over the unfolding and dissociation free energy landscape in vacuum. We examined wild-type SOD1 and six disease-related point-mutants by using tandem MS and ion-mobility MS (MS/MS-IMMS) coupled with increasing collisional activation potentials. For six of the seven SOD1 variants, increasing activation promoted dimers to transition through two unfolding events to access three gas-phase conformers before dissociating symmetrically into monomers with (as near as possible) equal charges. The exception was G37R, which proceeded only through the first unfolding transition, and displayed a much higher abundance of asymmetric products. We localise this effect to the formation of a new salt-bridge in the first activated conformation. To examine the data quantitatively, we generated a model of SOD1 gas phase unfolding and dissociation, and applied Arrhenius-type analysis to estimate the barriers on the corresponding free energy landscape. This reveals an increase in the barrier height to unfolding in G37R to be >5 kJ/mol<sup>-1</sup> higher than for the other variants, consistent with expectations for the strength of a salt-bridge. Our work demonstrates the importance of bond formation during the unfolding of proteins in vacuum, and provides a framework for comparing quantitatively the free energy landscape they explore upon activation.</p>

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