Complement membrane attack complex

 The membrane attack complex (MAC) is typically formed on the surface of intruding pathogenic bacterial cells as a result of the activation of the complement system, and it is one of the ultimate weapons of the immune system.

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Structure and function

It is composed of a complex of four complement proteins (C5b, C6, C7, and C8) which bind to the outer surface of the plasma membrane, and many copies of a fifth protein (C9) that hookup to one another, forming a ring in the membrane. C6-C9 all contain a common MACPF domain. ^[1] This region is homologous to cholesterol dependent cytolysins from Gram positive bacteria.^[2]

The ring structure acts as a tunnel through the membrane, allowing free diffusion of molecules in and out of the cell, which disrupts the internal environment of the cell, killing it quickly.

The MAC acts, analogically, like an oil rig by drilling into the cell and having the contents come out.

Initiation: C5-C7

The membrane attack complex is initiated when the complement protein, C5 convertase, cleaves C5 into C5a and C5b.

Another complement protein, C6, binds to C5b.

The C5bC6 complex is bound by C7.

This junction alters the configuration of the protein molecules exposing a hyrdrophobic site on C7 that allows the C7 to insert into the phospholipid bilayer of the pathogen.

Polymerization: C8-C9

Similar hydrophobic sites on C8 and C9 molecules are exposed when they bind to the complex, so they can also insert into the bilayer.

C8 is a complex made of two proteins C8 beta and C8 alpha-gamma.

C8 alpha-gamma has the hydrophobic area that inserts into the bilayer. C8 alpha-gamma induces the polymerization of 10-16 molecules of C9 into a pore-forming structure known as the membrane attack complex.

• It has a hydrophobic external face allowing it to associate with the lipid bilayer.

• It has a hydrophilic internal face to allow the passage of water.

Inhibition

CD59 acts to inhibit the complex.

References