Single cohesin molecules generate force by two distinct mechanisms.

Area of Science:

• Molecular biology
• Biophysics
• Structural biology

Background:

• Cohesin protein complexes are crucial for DNA spatial organization and loop extrusion.
• The precise mechanical workings of cohesin as a molecular machine remain largely unknown.

Purpose of the Study:

• To investigate the mechanical forces generated by single cohesin molecules during conformational changes.
• To elucidate the molecular mechanisms underlying cohesin's force generation and DNA interaction.

Main Methods:

• Utilizing single-molecule force measurements to quantify mechanical forces.
• Employing molecular dynamic simulations to model cohesin-DNA interactions and energy storage.

Main Results:

• Cohesin's SMC coiled coil bending, driven by thermal fluctuations, resists forces up to 1 pN (~32 nm displacement).
• ATP-dependent cohesin head engagement occurs in a single step (~10 nm), resisting forces up to 15 pN.
• Molecular dynamics simulations reveal energy storage in NIPBL during head engagement and release upon disengagement.

Conclusions:

• Single cohesin molecules generate force via two distinct mechanisms: thermal fluctuation-driven bending and ATP-dependent head engagement.
• A proposed model explains how these force-generating capabilities facilitate cohesin-DNA interactions and DNA loop extrusion.