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Structural Biology of the Membrane Attack Complex

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MACPF/CDC Proteins - Agents of Defence, Attack and Invasion

Part of the book series: Subcellular Biochemistry ((SCBI,volume 80))

Abstract

The complement system is an intricate network of serum proteins that mediates humoral innate immunity through an amplification cascade that ultimately leads to recruitment of inflammatory cells or opsonisation or killing of pathogens. One effector arm of this network is the terminal pathway of complement, which leads to the formation of the membrane attack complex (MAC) composed of complement components C5b, C6, C7, C8 and C9. Upon formation of C5 convertases via the classical or alternative pathways of complement activation, C5b is generated from C5 by proteolytic cleavage, nucleating a series of association and polymerisation reactions of the MAC-constituting complement components that culminate in pore formation of pathogenic membranes. Recent structures of MAC components and homologous proteins significantly increased our understanding of oligomerisation, membrane association and integration, shedding light onto the molecular mechanism of this important branch of the innate immune system.

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Abbreviations

Aa:

Amino acid

CCP:

Complement control protein repeat

CDCs:

Cholesterol-dependent cytolysins

CH1 and CH2:

Helical cluster 1 and helical cluster 2

CVF:

Cobra venom factor

d1, d3 and d4:

Domain 1, domain 3 and domain 4

EGF:

Epidermal growth factor-like repeat

FIM:

Factor I/membrane attack complex 6/7 module

LR:

Low density lipoprotein receptor class A repeat

MAC:

Membrane attack complex

MACPF:

Membrane attack complex/perforin

MBLs:

Manose binding lectins

MG:

Macroglobulin

PFPs:

Pore-forming proteins

poly-C9:

polymeric-C9

TMH1 and TMH2:

Transmembrane hairpin 1 and transmembrane hairpin 2

TS:

Thrombospondin type 1 repeat

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Acknowledgment

The Center for Chronic Immunodeficiency is supported by a Grant from the German Bundesministerium fü̈r Bildung und Forschung (BMBF 01EO0803). The author would like to thank the editors for the possibility to contribute to this volume.

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  1. Center for Chronic Immunodeficiency, University Medical Center Freiburg, Breisacher Straße 117, 79106, Freiburg, Germany

    Andreas F.-P. Sonnen & Philipp Henneke

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Correspondence to Andreas F.-P. Sonnen .

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  1. National Institute of Chemistry, Ljubljana, Slovenia, Laboratory for Molecular Biology and Nanobiotechnology, Ljubljana, Slovenia

    Gregor Anderluh

  2. Division of Structural Biology, University of Oxford Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom

    Robert Gilbert

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Sonnen, A.FP., Henneke, P. (2014). Structural Biology of the Membrane Attack Complex. In: Anderluh, G., Gilbert, R. (eds) MACPF/CDC Proteins - Agents of Defence, Attack and Invasion. Subcellular Biochemistry, vol 80. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8881-6_6

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