Structural basis of condensin II activation

Area of Science:

• Cell Biology
• Molecular Biology
• Structural Biology

Background:

• Condensin II is crucial for chromosome condensation but its activity is cell-cycle regulated.
• The mechanism keeping condensin II inactive during interphase is not well understood.

Purpose of the Study:

• To elucidate the structural basis for condensin II autoinhibition during interphase.
• To understand the regulation of condensin II activation.

Main Methods:

• Cryo-electron microscopy (cryo-EM) to determine high-resolution structures.
• Mass photometry to assess dimerization and complex formation.

Main Results:

• Nucleotide-free human condensin II forms a reversible dimer at physiological ionic strength.
• In the dimer, inhibitory elements (CAP-H2) are buried, and the CAP-D3 tail blocks key interactions.
• Nucleotide binding promotes monomerization and structural rearrangements, but autoinhibition persists until further regulatory events.

Conclusions:

• CAP-D3-dependent interactions mediate condensin II self-suppression.
• This autoinhibitory mechanism explains the cell-cycle-dependent activation of condensin II.
• The findings provide insights into the transition from an inactive to an active state, involving nucleotide binding and M18BP1 engagement.