scholarly journals Single Molecule Force Spectroscopy Reveals the Context Dependent Folding Pathway of the C-terminal Fragment of Top7

2021 ◽  
Author(s):  
Jiayu Li ◽  
Guojun Chen ◽  
Yabin Guo ◽  
Han Wang ◽  
Hongbin Li
Keyword(s):  
Single Molecule ◽  
De Novo ◽  
Force Spectroscopy ◽  
Atomic Level ◽  
Folding Pathway ◽  
Single Molecule Force Spectroscopy ◽  
Terminal Fragment ◽  
Folded Structure ◽  
Context Dependent

Top7 is a de novo designed protein with atomic level accuracy and shows a folded structure not found in nature. Previous studies showed that the folding of Top7 is not...

scholarly journals Single-molecule force spectroscopy reveals folding steps associated with hormone binding and activation of the glucocorticoid receptor

2018 ◽  
Vol 115 (46) ◽  
pp. 11688-11693 ◽  
Author(s):  
Thomas Suren ◽  
Daniel Rutz ◽  
Patrick Mößmer ◽  
Ulrich Merkel ◽  
Johannes Buchner ◽  
...  
Keyword(s):  
Free Energy ◽  
Glucocorticoid Receptor ◽  
Ligand Binding ◽  
Optical Tweezers ◽  
Single Molecule ◽  
Mechanical Load ◽  
Force Spectroscopy ◽  
Folding Pathway ◽  
Hormone Binding ◽  
Single Molecule Force Spectroscopy

The glucocorticoid receptor (GR) is a prominent nuclear receptor linked to a variety of diseases and an important drug target. Binding of hormone to its ligand binding domain (GR-LBD) is the key activation step to induce signaling. This process is tightly regulated by the molecular chaperones Hsp70 and Hsp90 in vivo. Despite its importance, little is known about GR-LBD folding, the ligand binding pathway, or the requirement for chaperone regulation. In this study, we have used single-molecule force spectroscopy by optical tweezers to unravel the dynamics of the complete pathway of folding and hormone binding of GR-LBD. We identified a “lid” structure whose opening and closing is tightly coupled to hormone binding. This lid is located at the N terminus without direct contacts to the hormone. Under mechanical load, apo-GR-LBD folds stably and readily without the need of chaperones with a folding free energy of 41 kBT (24 kcal/mol). The folding pathway is largely independent of the presence of hormone. Hormone binds only in the last step and lid closure adds an additional 12 kBT of free energy, drastically increasing the affinity. However, mechanical double-jump experiments reveal that, at zero force, GR-LBD folding is severely hampered by misfolding, slowing it to less than 1·s−1. From the force dependence of the folding rates, we conclude that the misfolding occurs late in the folding pathway. These features are important cornerstones for understanding GR activation and its tight regulation by chaperones.

scholarly journals A Tiny Toolbox

1997 ◽  
Vol 5 (7) ◽  
pp. 3-7
Author(s):  
Stephen W. Carmichael
Keyword(s):  
Atomic Force Microscope ◽  
Single Molecule ◽  
Recent Article ◽  
Single Molecules ◽  
Force Spectroscopy ◽  
Atomic Level ◽  
Single Molecule Force Spectroscopy ◽  
Binding Force ◽  
Atomic Force

A recent article by Matthias Rief, Filipp Oesterhelt. Berthold Heymann, and Hermann Gaub concluded with this sentence: "Single molecule force spectroscopy by AFM has proven to be a powerful addition to the nanoscopic piconewton toolbox," Everything about that conclusion is tiny. Clearly, the atomic force microscope (AFM) has given us a tool to examine structure at or near the atomic level. Earlier work from Gaub's laboratory, reviewed in this column, demonstrated that the AFM could directly measure the binding force between single molecules of biotin and avidin. This established that the AFM could be used as a tool to measure forces, not just observe structure. Their most recent experiments has added to this tiny toolbox.

Single molecule force spectroscopy reveals that a two-coordinate ferric site is critical for the folding of holo-rubredoxin

Nanoscale ◽  
2020 ◽  
Vol 12 (44) ◽  
pp. 22564-22573
Author(s):  
Jiayu Li ◽  
Hongbin Li
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Force Spectroscopy ◽  
Folding Pathway ◽  
Critical Importance ◽  
Spectroscopy Technique ◽  
Single Molecule Force Spectroscopy

The folding pathway of holo-rubredoxin was elucidated by using optical tweezers-based single molecule force spectroscopy technique. The results revealed the critical importance of the two-coordinate ferric site for the folding of holo-rubredoxin.

scholarly journals Single Molecule Force Spectroscopy of Siloxanes

2021 ◽  
Vol 714 (3) ◽  
pp. 032023
Author(s):  
Ling Chen ◽  
Liya Yang ◽  
Chunxia Wang ◽  
Ting Zhu
Keyword(s):  
Single Molecule ◽  
Force Spectroscopy ◽  
Single Molecule Force Spectroscopy

Pulling Genetic RNA out of Tobacco Mosaic Virus Using Single-Molecule Force Spectroscopy

2010 ◽  
Vol 132 (32) ◽  
pp. 11036-11038 ◽  
Author(s):  
Ningning Liu ◽  
Bo Peng ◽  
Yuan Lin ◽  
Zhaohui Su ◽  
Zhongwei Niu ◽  
...  
Keyword(s):  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Single Molecule ◽  
Force Spectroscopy ◽  
Single Molecule Force Spectroscopy
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