Complement system - CD46 (MCP)

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CD46 complement, also known as membrane cofactor protein (MCP), is a type 1 transmembrane glycoprotein which is widely expressed in host tissue, such as brain, kidney, skin, reproductive, eye, thyroid, liver and synovium. Now, it has become an important target for therapeutic antibody exploration. https://www.creative-biolabs.com/complement-therapeutics/drug-development-service-for-cd46-mcp.htm

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Complement system - CD46 MCP Introduction of CD46 MCP CD46 complement also known as membrane cofactor protein MCP is a type 1 transmembrane glycoprotein which in humans is encoded by the CD46 gene. CD46 is widely expressed in host tissue such as brain kidney skin reproductive eye thyroid liver and synovium where it acts as an inhibitory complement receptor to play the critical role in self-protection from the destructive action of autologous complement. Now it has become an important target for therapeutic antibody exploration. Structure of CD46 MCP Similar to CD55 CD46 also contains four short consensus repeat SCR domains also called CCP modules in the extracellular part followed by a region rich in serine threonine and proline STP region with three potential glycosylation sites. It is documented that SCR2 SCR3 and SCR4 are necessary for C3b/C4b binding whereas SCR1 and SCR2 are necessary for measles virus binding. Two differently glycosylated forms of MCP 58-68 kDa and 48-56 kDa have been reported and both contain O- and N-linked carbohydrate side chains with the larger form being more heavily sialylated. Fig.1 The Structure of the CD46 protein. Reynaud 2013

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Functions of CD46 MCP • Regulator of Complement Activation CD46 primarily functions as a cofactor for complement factor I in mediating cleavage of C3b. Also it participates in the cleavage of C4b resulting in the formation of C4c and C4d. It is notable that MCP preferentially inactivates the convertase of the alternative pathway. • Entry Receptor for Pathogens Identified as a receptor for measles virus CD46 can bind to human herpesvirus 6 Neisseria gonorrhoeaeand Neisseria meningitides bacteria and the M protein of Streptococcus. • Human T Cell Immunity Researches have revealed that CD46 can regulate the adaptive immune response acting as an additional costimulatory molecule for human T cells controlling T cell activation and inducing their differentiation into Tr1 cells. • Signal Transduction CD46 can mediate intracellular signal transduction such as calcium flux NO production and phosphorylation by cross-linking with antibodies or binding of natural ligands at the surface of several cell types.

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Fig.2 CD46 is involved in the entry of vesicular stomatitis virus G VSV-G-LVs. Lé vy 2017 Because of the importance in the regulation of complement activation control of pathogens entry and activation of T Cell Immunity CD46 has become a promising target for therapeutic antibody exploration and clinical trial. References 1. Reynaud J.M. Horvat B. Animal models for human herpesvirus 6 infection. Frontiers in microbiology. 2013 4: 174. 2. Lé vy C. et al. Measles virus envelope pseudotyped lentiviral vectors transduce quiescent human HSCs at an efficiency without precedent. Blood advances. 2017 123: 2088-2104.

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