An atomic model for the human septin hexamer by cryo-EM

Area of Science:

• Biochemistry
• Structural Biology
• Cell Biology

Background:

• Human septins are crucial proteins that assemble into hetero-oligomeric particles, forming filaments essential for cellular functions.
• Understanding septin assembly rules is vital, but high-resolution structures of intact particles have been challenging to obtain.

Purpose of the Study:

• To determine the high-resolution structure of a human septin hexameric particle using cryo-electron microscopy (cryo-EM).
• To elucidate the molecular interactions governing septin particle assembly and its implications for filament formation and membrane interactions.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was employed to obtain the structure of a SEPT2/6/7 hexameric particle.
• High-resolution crystal structures of individual septin subunits were fitted into the cryo-EM map to build a complete model.

Main Results:

• A cryo-EM structure of a human SEPT2/6/7 hexameric rod was determined at ~3.6 Å global resolution.
• The structure reveals specific interfaces, internal cavities possibly allowing subunit movement, and a central bending tendency due to SEPT7 homodimers.
• Detailed interactions, including those involving α-helices and polybasic/polyacidic regions, stabilize the particle structure.

Conclusions:

• The determined structure provides unprecedented insight into the assembly of human septin particles.
• The structural features, particularly the central bending, suggest a mechanism for septin filaments to interact with and influence membrane curvature.
• This work lays the foundation for understanding septin function in various cellular processes.