User:Immcarle125/Complement component 9

Complement component 9 (C9) is a MACPF protein involved in the complement system, a series of pathways a part of the innate immune system that aid in attacking pathogens and damaged cells. C9 can be activated through three different pathways: the classical complement activation pathway, the alternative complement pathway, and the lectin complement pathway. While these pathways begin with different steps, they converge with the initial formation C5 convertase and end with the polymerization of C9. The complement component 9 is activated by the interactions with additional complement components C5b, C6, C7 and C8. Once activated, the C9 induces pores on target cell membranes, causing lysis, as a member of the complement membrane attack complex (MAC).

There are 12-18 molecules of C9 in a single MAC they create a single-chain glycoprotein with a four domain structure. This structure allows the final step and formation of MAC that allows pore formation. Pore formation is essential in killing pathogens and infected cells. The lack of C9 can lead to LPS-induced acute shock and other clinical implications.

Structure
All C9s include 11 exons and 10 introns. 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 in Membrane Attack Complex
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 toMAC/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 and TMH2 regions. The formations of forms leads to the killing of foreign pathogens and infected host cells.

Clinical Significance
C9 plays a key role in completing the complement pathway as it leads to "anti-erythrocyte antibody-mediated hemolysis". Due to this significant function, when C9 is depleted, C5b-9 is not formed which leads to LPS-induced acute shock and less IL-1β is secreted. Without the secretion of IL-1β and additional pro-inflammatory cytokines in response to danger signals, C9 proves to be the essential in the LPS-inflammatory response and responding to microbial pathogens. The MAC is unable to form and therefore, more reoccurring infections can occur. The clinical impacts of a deficiency of C9 has led to acute Neisseria meningitidis.