Complement Component C9

Introduction of Complement Component C9

Complement component C9 is a multidomain protein containing an N-terminal type 1 TSP domain, an LDL receptor class A repeat, many potential transmembrane regions, and a C-terminal EGF-like domain. Hydrophilic analysis of the sequence showed that the N-terminal half of C9 was mainly hydrophilic, while the C-terminal part was hydrophobic. The amphiphilic structure of the primary structure is consistent with the known potential of polymeric C9 to penetrate lipid bilayers, resulting in the formation of transmembrane channels. C9 is mainly synthesized in liver cells, but can also be synthesized in other sites such as monocytes, fibroblasts and glial cells.

C9 is one of the components of the membrane attack complex (MAC), which completes a series of events leading to the destruction of the target membrane. MAC is assembled by sequentially binding complement components C5b, C6, C7, C8 and a variable number of C9 molecules to the target cell membrane. Up to 18 C9 molecules can bind to each C5b-8 complex, forming stable ion pores or channels on the membrane and causing lysis and death of the target cell upon complement activation.

Fig. 1 Assembly of the membrane attack complex (MAC). (Parsons et al., 2019)

Fig. 1 Assembly of the membrane attack complex (MAC). ¹

Complement Component C9 Deficiency

Like most other genetically determined complement defects, C9 deficiency is inherited as autosomal recessive heredity and it leads to the inability to assemble the MAC which in turn increases susceptibility to infection. Affected individuals usually have significantly reduced C9 levels. Because the function of C9 is to polymerize, which enlarges the small membrane lesions formed by C5-8, the MAC composed of C5b-8 can mediate hemolysis of sensitized red blood cells in the absence of C9. Patients with C9 deficiency have higher total hemolytic complement activity, and their serum has a certain bactericidal activity, although they have lower bactericidal activity compared to normal control serum.

Only a few patients with C9 deficiency have been identified in Westerners, but it is the most common complement deficiency in Japanese, with a prevalence of 1/1000. As with patients with other terminal component deficiency, patients with C9 deficiency have increased susceptibility to systemic meningococcal infections, and the risk of meningococcal infection in people with C9 deficiency is 700 times higher than in Japanese without C9 deficiency. A small number of patients develop Complement therapeutics for autoimmune disease, but the relationship between autoimmune diseases and C9 deficiency is unclear.

Creative Biolabs offers a full range of complement component C9-related services and products, including:

If you want more information, please feel free to contact us.

Reference

Parsons, Edward S., et al. "Single-molecule kinetics of pore assembly by the membrane attack complex." Nature communications 10.1 (2019): 2066.

Related Product

Featured C9 Products

For Research Use Only.