Structure of complement poly-C9 determined in projection by cryo-electron microscopy and single particle analysis

Area of Science:

• Immunology
• Structural Biology
• Biochemistry

Background:

• The membrane attack complex (MAC) forms pores in cell membranes during complement activation.
• The MAC is composed of complement components C5b through C9.
• The C9 component is believed to form the primary structure of the MAC.

Purpose of the Study:

• To investigate the structure of polymerized C9 (poly-C9) using cryo-electron microscopy.
• To determine the structural details of the poly-C9 complex and deduce the C9 monomer structure.

Main Methods:

• Cryo-electron microscopy (cryo-EM) and single particle analysis were employed.
• Correspondence analysis was used to identify variations in particle structure.
• 13-fold symmetry was utilized for particle averaging and structural determination.

Main Results:

• Polymerized C9 forms hollow cylinders with a dense inner ring and an outer rim with projections.
• The inner ring exhibits 13-fold symmetry and has a diameter of 113-181 Å.
• The structure suggests a rod-like C9 monomer oriented parallel to the cylinder axis.

Conclusions:

• Poly-C9 structures are consistent with the walls of the MAC.
• The study provides detailed structural insights into the C9 component of the MAC.
• The deduced C9 monomer structure aids in understanding pore formation mechanisms.