Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Unfolding a linker between helical repeats.

Vanessa Ortiz1, Steven O Nielsen, Michael L Klein

  • 1Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.

Journal of Molecular Biology
|May 18, 2005
PubMed
Summary

Mechanical stress on spectrin-like proteins causes unfolding. Steered molecular dynamics simulations reveal two pathways for linker unfolding, explaining single and tandem repeat unfolding observed in atomic force microscopy experiments.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Mechanobiological research fueling the advancement of mechanotherapy and mechanohealth.

Mechanobiology in medicine·2026
Same author

Cell confinement initiates a delayed but heritable loss of chromosomes.

Cell reports·2026
Same author

Cell confinement initiates a delayed but heritable loss of chromosomes.

bioRxiv : the preprint server for biology·2026
Same author

Lipid droplets are rigid and physically suppress phagocytosis, unless cell compression or stretching activates actomyosin.

Molecular biology of the cell·2026
Same author

Clustered macrophages cooperate to eliminate tumors via coordinated intrudopodia.

Proceedings of the National Academy of Sciences of the United States of America·2025
Same author

Matrix stiffness induces heritable changes in chromosome numbers, consistent with solid tumor heterogeneity.

bioRxiv : the preprint server for biology·2025

Area of Science:

  • Biophysics
  • Structural Biology
  • Computational Biology

Background:

  • Spectrin-like proteins (e.g., alpha-actinin, spectrin, dystrophin) feature three-helix bundle repeats linked by long helices.
  • These proteins are frequently exposed to mechanical stress.
  • Atomic force microscopy (AFM) reveals simultaneous unfolding of tandem repeats, suggesting cooperative transitions in linker helices.

Purpose of the Study:

  • To investigate the atomistic mechanisms of linker unfolding in spectrin repeats under mechanical stress.
  • To elucidate the pathways governing the mechanical response of spectrin-like protein linkers.

Main Methods:

  • Steered molecular dynamics (SMD) simulations.
  • Simulations performed in explicit water using tandem spectrin repeats.

Related Experiment Videos

  • Analysis of rate-dependent unfolding pathways.

    • Main Results:

    • Identified two distinct, rate-dependent unfolding pathways for alpha-actinin repeats.
    • One pathway involves linker unfolding, consistent with single-repeat unfolding observed in AFM.
    • A second pathway maintains linker integrity, explaining tandem repeat unfolding events.

    Conclusions:

    • Linker unfolding initiates with loop splaying, followed by destabilization and unwinding.
    • The unfolded linker mechanically decouples tandem repeats.
    • These findings provide molecular insights into the mechanical coupling and domain stability of spectrin family proteins.