scholarly journals Molecular mechanism of extreme mechanostability in a pathogen adhesin

Science ◽  
2018 ◽  
Vol 359 (6383) ◽  
pp. 1527-1533 ◽  
Author(s):  
Lukas F. Milles ◽  
Klaus Schulten ◽  
Hermann E. Gaub ◽  
Rafael C. Bernardi
Keyword(s):  
Single Molecule ◽  
Mechanical Stability ◽  
Force Spectroscopy ◽  
Covalent Bond ◽  
Binding Pocket ◽  
Peptide Backbone ◽  
Human Fibrinogen ◽  
Single Molecule Force Spectroscopy ◽  
Force Microscopy ◽  
Dynamics Simulations

High resilience to mechanical stress is key when pathogens adhere to their target and initiate infection. Using atomic force microscopy–based single-molecule force spectroscopy, we explored the mechanical stability of the prototypical staphylococcal adhesin SdrG, which targets a short peptide from human fibrinogen β. Steered molecular dynamics simulations revealed, and single-molecule force spectroscopy experiments confirmed, the mechanism by which this complex withstands forces of over 2 nanonewtons, a regime previously associated with the strength of a covalent bond. The target peptide, confined in a screwlike manner in the binding pocket of SdrG, distributes forces mainly toward the peptide backbone through an intricate hydrogen bond network. Thus, these adhesins can attach to their target with exceptionally resilient mechanostability, virtually independent of peptide side chains.

Going Vertical To Improve the Accuracy of Atomic Force Microscopy Based Single-Molecule Force Spectroscopy

ACS Nano ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 198-207 ◽  
Author(s):  
Robert Walder ◽  
William J. Van Patten ◽  
Ayush Adhikari ◽  
Thomas T. Perkins
Keyword(s):  
Atomic Force Microscopy ◽  
Single Molecule ◽  
Force Spectroscopy ◽  
Single Molecule Force Spectroscopy ◽  
Force Microscopy ◽  
Atomic Force

scholarly journals Streptavidin/biotin: Tethering geometry defines unbinding mechanics

2020 ◽  
Vol 6 (13) ◽  
pp. eaay5999 ◽  
Author(s):  
Steffen M. Sedlak ◽  
Leonard C. Schendel ◽  
Hermann E. Gaub ◽  
Rafael C. Bernardi
Keyword(s):  
Single Molecule ◽  
Conformational Changes ◽  
Energy Barrier ◽  
Mechanical Stability ◽  
Binding Pocket ◽  
Entire System ◽  
Shear Forces ◽  
Single Molecule Force Spectroscopy ◽  
Force Loading ◽  
Applied Forces

Macromolecules tend to respond to applied forces in many different ways. Chemistry at high shear forces can be intriguing, with relatively soft bonds becoming very stiff in specific force-loading geometries. Largely used in bionanotechnology, an important case is the streptavidin (SA)/biotin interaction. Although SA’s four subunits have the same affinity, we find that the forces required to break the SA/biotin bond depend strongly on the attachment geometry. With AFM-based single-molecule force spectroscopy (SMFS), we measured unbinding forces of biotin from different SA subunits to range from 100 to more than 400 pN. Using a wide-sampling approach, we carried out hundreds of all-atom steered molecular dynamics (SMD) simulations for the entire system, including molecular linkers. Our strategy revealed the molecular mechanism that causes a fourfold difference in mechanical stability: Certain force-loading geometries induce conformational changes in SA’s binding pocket lowering the energy barrier, which biotin has to overcome to escape the pocket.

Atomic force microscopy-based single-molecule force spectroscopy detects DNA base mismatches

Nanoscale ◽  
2019 ◽  
Vol 11 (37) ◽  
pp. 17206-17210 ◽  
Author(s):  
Wenjing Liu ◽  
Yourong Guo ◽  
Kaizhe Wang ◽  
Xingfei Zhou ◽  
Ying Wang ◽  
...  
Keyword(s):  
Single Molecule ◽  
Force Spectroscopy ◽  
Dna Origami ◽  
Single Molecule Force Spectroscopy ◽  
Force Microscopy ◽  
Atomic Force ◽  
Base Pair Mismatch ◽  
Dna Base ◽  
Single Base Pair ◽  
Target Molecules

AFM-based single-molecule-force spectroscopy is limited by low throughput. We introduce addressable DNA origami to study multiple target molecules at once. Target DNAs differing by only a single-base pair mismatch are clearly differentiated.

Single molecule force spectroscopy reveals that the oxidation state of cobalt ions plays an important role in enhancing the mechanical stability of proteins

Nanoscale ◽  
2019 ◽  
Vol 11 (42) ◽  
pp. 19791-19796 ◽  
Author(s):  
Jiahao Xia ◽  
Jiacheng Zuo ◽  
Hongbin Li
Keyword(s):  
Oxidation State ◽  
Single Molecule ◽  
Mechanical Stability ◽  
Force Spectroscopy ◽  
Metal Chelation ◽  
Single Molecule Force Spectroscopy ◽  
Cobalt Ions

The binding of Co(iii) to the bi-histidine metal chelation site significantly enhances protein's mechanical stability.

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