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Protein Folding01:25

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Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
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Protein and Protein Structure02:15

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Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
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Microfluidic Mixers for Studying Protein Folding
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Chain Sliding versus β-Sheet Formation upon Shearing Single α-Helical Coiled Coils.

Anna-Maria Tsirigoni1,2, Melis Goktas1, Zeynep Atris1,2

  • 1Max Planck Institute of Colloids and Interfaces, Mechano(bio)chemistry, Am Mühlenberg 1, 14476, Potsdam, Germany.

Macromolecular Bioscience
|March 2, 2023
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Summary
This summary is machine-generated.

Synthetic coiled coils (CCs) can mimic natural materials

Keywords:
alpha-beta transitionalpha-helicesbeta-sheetscoiled coilsmolecular dynamics simulationsprotein mechanicssingle-molecule force spectroscopy

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Area of Science:

  • Biomaterials Science
  • Structural Biology
  • Computational Chemistry

Background:

  • Coiled coils (CCs) are crucial protein structures that dictate the mechanical properties of biological materials.
  • These materials can undergo a force-induced transition from alpha-helices to beta-sheets (αβT), enhancing their strength.
  • Previous simulations suggest this αβT is dependent on CC length and pulling speed.

Purpose of the Study:

  • To investigate if de novo designed CCs can replicate the force-induced αβT observed in natural CCs.
  • To determine the mechanical response and rupture forces of synthetic CCs with varying lengths (four to seven heptads).
  • To explore the influence of pulling speed on the αβT phenomenon in CCs.

Main Methods:

  • Utilized de novo designed coiled coils with lengths ranging from four to seven heptads.
  • Employed single-molecule force spectroscopy to mechanically load CCs in shear geometry.
  • Conducted molecular dynamics simulations at different pulling speeds (0.01 nm/ns and 0.001 nm/ns).

Main Results:

  • Simulations at high pulling speeds (0.01 nm/ns) induced β-sheet formation in five- and six-heptad CCs, increasing mechanical strength.
  • The αβT transition was less likely at lower pulling speeds (0.001 nm/ns) and not observed in force spectroscopy experiments.
  • In shear geometry, β-sheet formation competed with interchain sliding, limiting the transition.

Conclusions:

  • Synthetic coiled coils can be designed to exhibit force-induced transitions, mimicking natural biomaterials.
  • The αβT phenomenon in CCs is highly dependent on loading conditions, including pulling speed and geometry.
  • Efficient β-sheet formation requires specific loading conditions that prevent interchain sliding, such as tensile geometries or higher-order assemblies.