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Coiled-coil intermediate filament stutter instability and molecular unfolding
Melis Arslan1, Zhao Qin, Markus J Buehler
1Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Computer Methods in Biomechanics and Biomedical Engineering
|April 26, 2011
Summary
The stutter region in intermediate filaments (IFs) is more stable unfolded, causing structural instability. This finding impacts understanding of cell mechanics and protein unfolding under deformation.
Area of Science:
- Cell biology
- Biophysics
- Structural biology
Background:
- Intermediate filaments (IFs) form the eukaryotic cytoskeleton, crucial for cell mechanics.
- IFs assemble from coiled-coil alpha-helical dimers with structural discontinuities.
- The 'stutter' region is a sequence variation within the coiled-coil domain.
Purpose of the Study:
- To investigate the structural stability of the stutter region in vimentin IFs.
- To determine the impact of the stutter on the nanomechanics of intermediate filaments.
Main Methods:
- Explicit water molecular dynamics simulations.
- Well-tempered metadynamics.
Main Results:
- The stutter region of vimentin IFs is more stable in a non-alpha-helical, unfolded state.
- This local unfolding causes global structural disturbance and affects nanomechanics.
- The stutter exhibits enhanced unfolding tendency and reduced bending stiffness.
Conclusions:
- The stutter region is intrinsically less stable than previously assumed.
- It acts as a initiation site for molecular bending and unfolding.
- Findings provide insights into the mechanical properties and instability of intermediate filaments.
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