Incorporation of human complement C8 into the membrane attack complex is mediated by a binding site located within the C8beta MACPF domain

Molecular Immunology
Charity Brannen, James M Sodetz

Abstract

Human C8 is one of five complement components (C5b, C6, C7, C8, C9) that interact to form the membrane attack complex (MAC). C8 is an oligomeric protein composed of a disulfide-linked C8alpha-gamma heterodimer and a noncovalently associated C8beta chain. C8alpha and C8beta are homologous; both contain N- and C-terminal modules and an intervening approximately 40 kDa segment referred to as the membrane attack complex/perforin (MACPF) domain. C8beta participates in at least two binding interactions. It has a high affinity binding site for C8alpha, which facilitates its interaction with C8alpha-gamma. C8beta also mediates incorporation of C8 into the MAC by binding to C5b-7, an intermediate in the MAC assembly pathway. Little is known about the location or properties of the respective binding sites on C8beta. In this study, the MACPF domain of C8beta (betaMACPF) was expressed in Escherichia coli and its role in binding C8alpha and C5b-7 examined. Recombinant betaMACPF was shown to bind C8alpha-gamma in solution and form a noncovalent complex (betaMACPF*C8alpha-gamma) that exhibited C8 hemolytic activity. betaMACPF was also capable of binding independently to erythrocytes carrying C5b-7. Subsequent addition of C8alpha-gamma and C9 ...Continue Reading

Citations

Apr 2, 2011·The Journal of Biological Chemistry·Leslie L LovelaceLukasz Lebioda
Nov 16, 2010·Journal of Molecular Biology·Doryen BubeckSusan M Lea
Apr 1, 2016·PloS One·Nehemiah ZewdeDimitrios Morikis
Aug 28, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Dennis J DoorduijnDani A C Heesterbeek

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