Coiled-coil intermediate filament stutter instability and molecular unfolding

Melis Arslana, Zhao Qin, Markus J. Buehler

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Intermediate filaments (IFs) are the key components of cytoskeleton in eukaryotic cells and are critical for cell mechanics. The building block of IFs is a coiled-coil alpha-helical dimer, consisting of several domains that include linkers and other structural discontinuities. One of the discontinuities in the dimer's coiled-coil region is the so-called 'stutter' region. The stutter is a region where a variation of the amino acid sequence pattern from other parts of the alpha-helical domains of the protein is found. It was suggested in earlier works that due to this sequence variation, the perfect coiled-coil arrangement ceases to exist. Here, we show using explicit water molecular dynamics and well-tempered metadynamics that for the coil2 domain of vimentin IFs the stutter is more stable in a non-alpha-helical, unfolded state. This causes a local structural disturbance in the alpha helix, which has a global effect on the nanomechanics of the structure. Our analysis suggests that the stutter features an enhanced tendency to unfolding even under the absence of external forces, implying a much greater structural instability than previously assumed. As a result it features a smaller local bending stiffness than other segments and presents a seed for the initiation of molecular bending and unfolding at large deformation.

Original languageEnglish (US)
Pages (from-to)483-489
Number of pages7
JournalComputer Methods in Biomechanics and Biomedical Engineering
Volume14
Issue number5
DOIs
StatePublished - 2011
Externally publishedYes

Keywords

  • Alpha helix
  • Coiled coil
  • Intermediate filaments
  • Materiomics
  • Nanomechanics
  • Protein

ASJC Scopus subject areas

  • Bioengineering
  • Biomedical Engineering
  • Human-Computer Interaction
  • Computer Science Applications

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