Complement: Terminal Pathway

James M Sodetz, University of South Carolina, South Carolina, USA
Mnason E Plumb, University of South Carolina, South Carolina, USA

Published online: September 2005

DOI: 10.1038/npg.els.0003977

Terminal pathway of complement refers to the sequence of interactions between components C5b, C6, C7, C8 and C9 that leads to the production of a ‘membrane attack complex’ possessing the ability to disrupt cell membranes.

Keywords: complement; lysis; membrane; bacteria; lipocalins

Figure 1. Modular structure of MAC protein family. Modules are labelled as follows: T1, thrombospondin type I; LA, low-density lipoprotein receptor class A; EG, epidermal growth factor; CP, complement control protein and FM, factor I module. MACPF is an extended region of sequence similarity found within all family members and perforin. Numbers correspond to amino acid residues in the mature proteins. Possible N-glycosylation sites are identified by (*). C8 is linked to Cys164 in C8.
Figure 2. Assembly of MAC. Topographical model of MAC formation on a membrane bilayer. The ¢ and chains of C5b and the and chains of C8 are represented as disulfide-linked dimers. C9 within MAC is shown as a polymer (poly C9) composed of an arbitrary number (n) of C9 monomers.
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 References
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    Byrne GW, McCurry KR, Martin MJ, et al. (1997) Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage. Transplantation 63: 149–155.
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    Esser AF (1994) The membrane attack complex of complement: assembly, structure and cytotoxic activity. Toxicology 87: 229–247.
    Flower D, North ACT and Sansom CE (2000) The lipocalin protein family: structural and sequence overview. Biochimica et Biophysica Acta 1482: 9–24.
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    book Mold C (1998) "Cellular responses to the membrane attack complex". In: Volanakis JE and Frank MM (eds) The Human Complement System in Health and Disease, pp. 309–325. New York: Marcel Dekker.
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    Musingarimi P, Plumb ME and Sodetz JM (2002) Interaction between the C8– and C8 subunits of human complement C8: role of the C8N-terminal thrombospondin type 1 module and membrane attack complex/perforin domain. Biochemistry 41: 11255–11260.
    Ortlund E, Parker CL, Schreck SF, et al. (2002) Crystal structure of human complement protein C8 at 1.Å resolution reveals a lipocalin fold and a distinct ligand binding site. Biochemistry 41: 7030–7037.
    book Plumb ME and Sodetz JM (1998) "Proteins of the membrane attack complex". In: Volanakis JE and Frank MM (eds) The Human Complement System in Health and Disease, pp. 119–148. New York: Marcel Dekker.
    Schreck SF, Parker CP, Plumb ME and Sodetz JM (2000) Human complement protein C8. Biochimica et Biophysica Acta 1482: 199–208.
    Scibek JJ, Plumb ME and Sodetz JM (2002) Binding of human complement C8 to C9: role of the N-terminal modules in the C8 subunit. Biochemistry 41: 14546–14551.
    Wang Y, Bjes ES and Esser AF (2000) Molecular aspects of complement-mediated bacterial killing: periplasmic conversion of C9 from a protoxin to a toxin. Journal of Biological Chemistry 275: 4687–4692.
 Further Reading
    book Åkerstrom B, Flower D and Salier JP (eds) (2000) Lipocalins. Biochimica et Biophysica Acta 1482: 1–356.
    ePath http://www.jenner.ac.uk/lipocalin/lipocalins.htm. Provides information on the structure and function of lipocalins.
    Liszewski MK, Farries TC, Lublin DM, Rooney IA and Atkinson JP (1996) Control of the complement system. Advances in Immunology 61: 201–283.
    book Morgan BP (1990) Complement: Clinical Aspects and Relevance to Disease. London: Academic Press.
    book Morikis D and Lambris JD (2005) Structural Biology of the Complement System. New York: Marcel Dekker.
    book Morley BJ and Walport MJ (eds) (2000) The Complement FactsBook. London: Academic Press.
    book Parker CM (ed.) (1992) Current Topics in Microbiology and Immunology, Vol. 178, "Membrane Defenses Against Attack by Complement and Perforins". Berlin: Springer-Verlag.
    Platt JL (1998) New directions for organ transplantation. Nature 392 (Suppl.): 11–17.
    book Szebeni J (ed.) (2004) The Component System: Novel Roles in Health and Disease. Boston: Kluwer.
    book Volanakis JE and Frank MM (eds) (1998) The Human Complement System in Health and Disease. New York: Marcel Dekker.
    Würzner R, Orren A and Lachman PJ (1992) Inherited deficiencies of the terminal components of human complement. Immunodeficiency Reviews 3: 123–147.

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Article Title: Complement: Terminal Pathway
 
How to Cite close
Sodetz, James M, and Plumb, Mnason E(Sep 2005) Complement: Terminal Pathway. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003977]