Mechanically unfolding the small, topologically simple protein L

Area of Science:

• Biophysics and Structural Biology
• Mechanobiology
• Protein Folding and Dynamics

Background:

• Beta-sheet proteins generally show greater resistance to mechanical forces compared to alpha-helical proteins.
• Previous studies hypothesized that parallel, hydrogen-bonded beta-strands at protein termini confer maximal mechanical strength.

Purpose of the Study:

• To test the hypothesis that specific beta-strand arrangements enhance mechanical strength.
• To investigate the mechanical properties and unfolding mechanisms of protein L, a topologically strong protein domain.

Main Methods:

• Experimental measurement of the mechanical resistance of protein L pentamers.
• Molecular dynamics simulations to analyze the energy landscape and unfolding pathways of protein L.

Main Results:

• Protein L pentamers demonstrated significant resistance to mechanical deformation across various extension rates.
• Simulations revealed a restricted energy landscape for protein L unfolding, occurring via shearing of structural units.
• Protein L unfolds via a mechanism similar to ubiquitin but at a lower force, suggesting conserved mechanisms within fold families.

Conclusions:

• Protein L's mechanical unfolding mechanism is conserved within its fold family.
• Protein topology and hydrogen-bonded clamps are crucial for mechanical strength, with hydrophobic interactions also playing a significant role.