Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force...

Area of Science:

• Molecular Biology
• Biophysics
• Structural Biology

Background:

• Condensin complex compacts chromatin via DNA-loop extrusion.
• Mechanisms like scrunching and loop-capture involve DNA binding to the hinge domain.
• The precise interaction of the hinge domain with double-strand (ds) DNA is unknown.

Purpose of the Study:

• To elucidate the molecular mechanism of dsDNA binding to the condensin hinge domain.
• To model the hinge domain's conformational changes and their role in DNA binding.
• To investigate how hinge dynamics regulate DNA-loop extrusion.

Main Methods:

• Atomic force microscopy (AFM) imaging of budding yeast condensin holo-complex.
• Coarse-grained molecular dynamics (MD) simulations.
• Modeling of open and closed hinge conformations and dsDNA binding.

Main Results:

• dsDNA binds to the outside surface of the closed hinge.
• dsDNA binds to both outside and inside surfaces of the open hinge.
• The hinge domain can close around dsDNA bound to its inside surface.

Conclusions:

• Hinge domain conformational changes are critical for regulating dsDNA binding.
• These dynamics likely play a key role in condensin-mediated DNA-loop extrusion.
• The study provides a structural basis for understanding condensin's function in genome organization.