Imperial College London
Alternate

DrArmandoDel Rio Hernandez

Faculty of Engineering, Department of Bioengineering

Reader in Cellular and Molecular Mechanotransduction
 
 
 
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Contact

 

+44 (0)20 7594 5187a.del-rio-hernandez

 
 
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Location

 

308Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mykuliak:2018:10.1371/journal.pcbi.1006126,
author = {Mykuliak, V and Haining, A and von, Essen M and Del, Rio Hernandez AE and Hytonen, V},
doi = {10.1371/journal.pcbi.1006126},
journal = {PLoS Computational Biology},
title = {Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin},
url = {http://dx.doi.org/10.1371/journal.pcbi.1006126},
volume = {14},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Mechanical stability is a key feature in the regulation of structural scaffolding proteins and their functions. Despite the abundance of α-helical structures among the human proteome and their undisputed importance in health and disease, the fundamental principles of their behavior under mechanical load are poorly understood. Talin and α-catenin are two key molecules in focal adhesions and adherens junctions, respectively. In this study, we used a combination of atomistic steered molecular dynamics (SMD) simulations, polyprotein engineering, and single-molecule atomic force microscopy (smAFM) to investigate unfolding of these proteins. SMD simulations revealed that talin rod α-helix bundles as well as α-catenin α-helix domains unfold through stable 3-helix intermediates. While the 5-helix bundles were found to be mechanically stable, a second stable conformation corresponding to the 3-helix state was revealed. Mechanically weaker 4-helix bundles easily unfolded into a stable 3-helix conformation. The results of smAFM experiments were in agreement with the findings of the computational simulations. The disulfide clamp mutants, designed to protect the stable state, support the 3-helix intermediate model in both experimental and computational setups. As a result, multiple discrete unfolding intermediate states in the talin and α-catenin unfolding pathway were discovered. Better understanding of the mechanical unfolding mechanism of α-helix proteins is a key step towards comprehensive models describing the mechanoregulation of proteins.
AU  - Mykuliak,V
AU  - Haining,A
AU  - von,Essen M
AU  - Del,Rio Hernandez AE
AU  - Hytonen,V
DO  - 10.1371/journal.pcbi.1006126
PY  - 2018///
SN  - 1553-734X
TI  - Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin
T2  - PLoS Computational Biology
UR  - http://dx.doi.org/10.1371/journal.pcbi.1006126
UR  - http://hdl.handle.net/10044/1/59233
VL  - 14
ER  -
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