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About the Authors:
Vasyl V. Mykuliak
Contributed equally to this work with: Vasyl V. Mykuliak, Alexander William M. Haining, Magdaléna von Essen
Roles Data curation, Investigation, Visualization, Writing - original draft
Affiliation: Faculty of Medicine and Life Sciences and BioMediTech, University of Tampere, Finland and Fimlab Laboratories, Tampere, Finland
Alexander William M. Haining
Contributed equally to this work with: Vasyl V. Mykuliak, Alexander William M. Haining, Magdaléna von Essen
Roles Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing - original draft
Affiliation: Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, United Kingdom
ORCID http://orcid.org/0000-0001-8997-2882
Magdaléna von Essen
Contributed equally to this work with: Vasyl V. Mykuliak, Alexander William M. Haining, Magdaléna von Essen
Roles Conceptualization, Investigation, Visualization, Writing - original draft
Affiliation: Faculty of Medicine and Life Sciences and BioMediTech, University of Tampere, Finland and Fimlab Laboratories, Tampere, Finland
Armando del Río Hernández
Roles Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Validation, Writing - review & editing
* E-mail: [email protected] (AdRH); [email protected] (VPH)
Affiliation: Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, United Kingdom
ORCID http://orcid.org/0000-0001-5062-8910
Vesa P. Hytönen
Roles Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Validation, Writing - review & editing
* E-mail: [email protected] (AdRH); [email protected] (VPH)
Affiliation: Faculty of Medicine and Life Sciences and BioMediTech, University of Tampere, Finland and Fimlab Laboratories, Tampere, Finland
ORCID http://orcid.org/0000-0002-9357-1480Abstract
Mechanical stability is a key feature in the regulation of structural scaffolding proteins and their functions. Despite the abundance of [alpha] -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 [alpha] -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 [alpha] -helix bundles as well as [alpha] -catenin [alpha] -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...