Complement membrane attack complex
Encyclopedia
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
ic bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s as a result of the activation of the alternative pathway
Alternative complement pathway
The alternative pathway of the complement system is an innate component of the immune system's natural defense against infections, which can operate without antibody participation....
of the complement system
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
, and it is one of the effector proteins of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. The membrane-attack complex (MAC) forms transmembrane channels. These channels disrupt the phospholipid bilayer of target cells, leading to cell lysis and death.
A number of proteins participate in the assembly of the MAC. Freshly activated C5b binds to C6 to form a C5b-6 complex, then to C7 forming the C5b-7 complex. The C5b-7 complex binds to C8, which is composed of three chains (alpha, beta, and gamma), thus forming the C5b-8 complex. C5b-8 subsequently binds to C9 and acts as a catalyst in the polymerization of C9. Active MAC has a subunit composition of C5b-C6-C7-C8-C9{n}.
Structure and function
It is composed of a complex of four complement proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s (C5b, C6, C7, and C8) that 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
MACPF
The MACPF protein superfamily is named after a domain that is common to the Membrane Attack Complex proteins of complement and perforin . Many members of this protein family are important eukaryote pore forming toxins....
domain. This region is homologous
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
to cholesterol-dependent cytolysin
Cytolysin
Cytolysin refers to the substance or antibody elaborated by microorganisms, plants or animals that is specifically toxic to individual cells, in many cases causing their dissolution through lysis. Cytolysins that have a specific action for certain cells are named accordingly...
s from Gram-positive bacteria.
The ring structure formed by C9 is a pore in the membrane that allows free diffusion
Diffusion
Molecular diffusion, often called simply diffusion, is the thermal motion of all particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size of the particles...
of molecules in and out of the cell. If enough pores form, the cell is no longer able to survive.
Initiation: C5-C7
The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5Complement component 5
Complement component 5 is a protein that in humans is encoded by the C5 gene.Complement component 5 is involved in the complement system. It is cleaved into C5a and C5b:* C5a plays an important role in chemotaxis....
into C5a and C5b.
Another complement protein, C6
Complement component 6
Complement component 6 is a protein that in humans is encoded by the C6 gene.Complement component 6 is a protein involved in the complement system. It is part of the membrane attack complex which can insert into the cell membrane and cause cell to lyse....
, binds to C5b.
The C5bC6 complex is bound by C7
Complement component 7
Complement component 7 is a protein involved in the complement system....
.
This junction alters the configuration of the protein molecules exposing a hydrophobic site on C7 that allows the C7 to insert into the phospholipid bilayer of the pathogen.
Polymerization: C8-C9
Similar hydrophobic sites on C8C8 complex
Complement component 8 is a protein involved in the complement system. A hereditary deficiency of C8 can result in increased susceptibility to Neisseria infections, such as meningitis and gonorrhea.-References:...
and C9
Complement component 9
Complement component 9 is a protein involved in the complement system....
molecules are exposed when they bind to the complex, so they can also insert into the bilayer.
C8 is a complex made of the 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 bilayerLipid bilayerThe lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
.
- It has a hydrophilic internal face to allow the passage of water.