Soluble Membrane Attack Complex: Biochemistry and Immunobiology

The soluble membrane attack complex (sMAC, a.k.a., sC5b-9 or TCC) is generated on activation of complement and contains the complement proteins C5b, C6, C7, C8, C9 together with the regulatory proteins clusterin and/or vitronectin. sMAC is a member of the MACPF/cholesterol-dependent-cytolysin superf...

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Main Authors: Scott R. Barnum, Doryen Bubeck, Theresa N. Schein
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-11-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2020.585108/full
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author Scott R. Barnum
Doryen Bubeck
Theresa N. Schein
author_facet Scott R. Barnum
Doryen Bubeck
Theresa N. Schein
author_sort Scott R. Barnum
collection DOAJ
description The soluble membrane attack complex (sMAC, a.k.a., sC5b-9 or TCC) is generated on activation of complement and contains the complement proteins C5b, C6, C7, C8, C9 together with the regulatory proteins clusterin and/or vitronectin. sMAC is a member of the MACPF/cholesterol-dependent-cytolysin superfamily of pore-forming molecules that insert into lipid bilayers and disrupt cellular integrity and function. sMAC is a unique complement activation macromolecule as it is comprised of several different subunits. To date no complement-mediated function has been identified for sMAC. sMAC is present in blood and other body fluids under homeostatic conditions and there is abundant evidence documenting changes in sMAC levels during infection, autoimmune disease and trauma. Despite decades of scientific interest in sMAC, the mechanisms regulating its formation in healthy individuals and its biological functions in both health and disease remain poorly understood. Here, we review the structural differences between sMAC and its membrane counterpart, MAC, and examine sMAC immunobiology with respect to its presence in body fluids in health and disease. Finally, we discuss the diagnostic potential of sMAC for diagnostic and prognostic applications and potential utility as a companion diagnostic.
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spelling doaj.art-fb29b4d5d6d84c17b6b3397d9251d18d2022-12-21T18:14:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-11-011110.3389/fimmu.2020.585108585108Soluble Membrane Attack Complex: Biochemistry and ImmunobiologyScott R. Barnum0Doryen Bubeck1Theresa N. Schein2CNine Biosolutions, LLC, Birmingham, AL, United StatesDepartment of Life Sciences, Imperial College London, London, United KingdomCNine Biosolutions, LLC, Birmingham, AL, United StatesThe soluble membrane attack complex (sMAC, a.k.a., sC5b-9 or TCC) is generated on activation of complement and contains the complement proteins C5b, C6, C7, C8, C9 together with the regulatory proteins clusterin and/or vitronectin. sMAC is a member of the MACPF/cholesterol-dependent-cytolysin superfamily of pore-forming molecules that insert into lipid bilayers and disrupt cellular integrity and function. sMAC is a unique complement activation macromolecule as it is comprised of several different subunits. To date no complement-mediated function has been identified for sMAC. sMAC is present in blood and other body fluids under homeostatic conditions and there is abundant evidence documenting changes in sMAC levels during infection, autoimmune disease and trauma. Despite decades of scientific interest in sMAC, the mechanisms regulating its formation in healthy individuals and its biological functions in both health and disease remain poorly understood. Here, we review the structural differences between sMAC and its membrane counterpart, MAC, and examine sMAC immunobiology with respect to its presence in body fluids in health and disease. Finally, we discuss the diagnostic potential of sMAC for diagnostic and prognostic applications and potential utility as a companion diagnostic.https://www.frontiersin.org/articles/10.3389/fimmu.2020.585108/fullcomplementsoluble membrane attack complexsC5b-9cholesterol-dependent cytolysinsMACdiagnostics
spellingShingle Scott R. Barnum
Doryen Bubeck
Theresa N. Schein
Soluble Membrane Attack Complex: Biochemistry and Immunobiology
Frontiers in Immunology
complement
soluble membrane attack complex
sC5b-9
cholesterol-dependent cytolysins
MAC
diagnostics
title Soluble Membrane Attack Complex: Biochemistry and Immunobiology
title_full Soluble Membrane Attack Complex: Biochemistry and Immunobiology
title_fullStr Soluble Membrane Attack Complex: Biochemistry and Immunobiology
title_full_unstemmed Soluble Membrane Attack Complex: Biochemistry and Immunobiology
title_short Soluble Membrane Attack Complex: Biochemistry and Immunobiology
title_sort soluble membrane attack complex biochemistry and immunobiology
topic complement
soluble membrane attack complex
sC5b-9
cholesterol-dependent cytolysins
MAC
diagnostics
url https://www.frontiersin.org/articles/10.3389/fimmu.2020.585108/full
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AT theresanschein solublemembraneattackcomplexbiochemistryandimmunobiology