Complement component 9 (C9) is a

MACPF The Membrane Attack Complex/Perforin (MACPF) superfamily, sometimes referred to as the MACPF/CDC superfamily, is named after a domain that is common to the membrane attack complex (MAC) proteins of the complement system (C6, C7, C8α, C8β a ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

involved in the

complement system The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and ...

, which is part of the

innate immune system The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is th ...

. Once activated, about 12-18 molecules of C9 polymerize to form pores in target

cell membranes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (th ...

, causing

lysis Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...

and cell death. C9 is one member of the

complement membrane attack complex The membrane attack complex (MAC) or terminal complement complex (TCC) is a complex of proteins typically formed on the surface of pathogen cell membranes as a result of the activation of the host's complement system, and as such is an effector ...

(MAC), which also includes complement components C5b, C6, C7 and C8. The formation of the MAC occurs through three distinct pathways: the classical, alternative, and lectin pathways. Pore formation by C9 is an important way that bacterial cells are killed during an infection, and the target cell is often covered in multiple MACs. The clinical impact of a deficiency in C9 is an infection with the gram-negative bacterium ''

Neisseria meningitidis ''Neisseria meningitidis'', often referred to as meningococcus, is a Gram-negative bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. The bacterium is referred to as ...

.''

Structure

C9 genes include 11

exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequenc ...

and 10

introns An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene ...

when found in fish. In fish, the liver is the site where the majority of complement components are produced and expressed, but C9 can also be found in other tissues. It is a single-chain glycoprotein with a four domain structure arranged in a globular bundle.

Pore formation

MAC formation starts with the assembly of a tetrameric complex with the complement components C6, C7, C8, and C5b. The final step of MAC on target cell surfaces involves the polymerization of C9 molecules bound to C5b8 forming C5b-9. C9 molecules allow cylindrical, asymmetrical transmembrane pores to form. The overall complex belongs to MAC/perforin-like (MACPF)/CDC superfamily. Pore formation involves binding the C9 molecules to the target membrane, membrane molecules forming a pre-pore shape, and conformational change in the TMH1, the first transmembrane region, and TMH2, the second transmembrane region. The formations of pores leads to the killing of foreign pathogens and infected host cells.

Relation to aging process

C9 was found to be the most strongly under expressed serum protein in men who achieved longevity, compared to men who did not.

References

External links

*
PDBe-KB
provides an overview of all the structure information available in the PDB for Human Complement component C9 Complement system {{immunology-stub