Disulfide bonds-driven assembly and structural complexity of PTX3: High-resolution structures insights into...

Area of Science:

• Immunology
• Structural Biology
• Biochemistry

Background:

• Pentraxin-3 (PTX3) is a key pattern-recognition molecule involved in innate immunity.
• PTX3 plays critical roles in pathogen recognition and complement system activation.
• The structural mechanisms governing PTX3 oligomerization and function remain largely unknown.

Purpose of the Study:

• To elucidate the structural basis of Pentraxin-3 (PTX3) oligomerization.
• To understand how PTX3 assembly influences its immune functions, particularly complement activation.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was utilized to determine PTX3 structures.
• High-resolution structures of PTX3 octamers and tetramers were resolved.
• Medium-resolution structures of PTX3 dimers and hexamers were also obtained.

Main Results:

• PTX3 oligomerization is driven by dimeric units stabilized by C-terminal disulfide bonds.
• N-terminal disulfide bonds further facilitate the assembly into larger PTX3 oligomers.
• A hierarchical assembly process was identified, crucial for classical complement pathway activation.

Conclusions:

• The study reveals the detailed structural mechanisms of PTX3 oligomerization.
• Hierarchical assembly of PTX3 is essential for its role in the complement system.
• These findings provide a foundation for developing PTX3-targeted therapeutics.