Structure of Human C8 Protein Provides Mechanistic Insight into Membrane Pore Formation by Complement*

@article{Lovelace2011StructureOH,
  title={Structure of Human C8 Protein Provides Mechanistic Insight into Membrane Pore Formation by Complement*},
  author={Leslie L. Lovelace and Christopher L. Cooper and James M. Sodetz and Lukasz Lebioda},
  journal={The Journal of Biological Chemistry},
  year={2011},
  volume={286},
  pages={17585 - 17592}
}
C8 is one of five complement proteins that assemble on bacterial membranes to form the lethal pore-like “membrane attack complex” (MAC) of complement. The MAC consists of one C5b, C6, C7, and C8 and 12–18 molecules of C9. C8 is composed of three genetically distinct subunits, C8α, C8β, and C8γ. The C6, C7, C8α, C8β, and C9 proteins are homologous and together comprise the MAC family of proteins. All contain N- and C-terminal modules and a central 40-kDa membrane attack complex perforin (MACPF… Expand
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TLDR
The crystal structure of the human C8 alpha MACPF domain disulfide-linked to C8 gamma (alphaMACPF-gamma) at 2.15 A resolution has been determined and conservation of several key glycine residues known to be important for refolding and pore formation by CDCs are observed. Expand
Incorporation of human complement C8 into the membrane attack complex is mediated by a binding site located within the C8beta MACPF domain.
TLDR
Results indicate the principal binding sites for C8alpha and C5b-7 are located within this domain, and that C8beta binding specificity is not determined by the N- and C-terminal modules. Expand
Structure of C8α-MACPF Reveals Mechanism of Membrane Attack in Complement Immune Defense
TLDR
The crystal structure of the MACPF domain of complement component C8α is determined and it is shown that it is structurally homologous to the bacterial, pore-forming, cholesterol-dependent cytolysins, implying that these mammalian and bacterial cytolytic proteins share a common mechanism of membrane insertion. Expand
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TLDR
Human C8 subunits were examined for their ability to support complement-mediated killing of Gram-negative bacteria and it is suggested that C8 alpha and C8 beta have correspondingly similar roles in MAC-mediated lysis of erythrocytes and bacterial killing. Expand
Crystal structure of human complement protein C8gamma at 1.2 A resolution reveals a lipocalin fold and a distinct ligand binding site.
TLDR
The three-dimensional structure of recombinant C8gamma was determined by X-ray diffraction to 1.2 A resolution and displays a typical lipocalin fold forming a calyx with a distinct binding pocket that is indicative of a ligand-binding function for C8Gamma. Expand
Complement Components C5 and C7: Recombinant Factor I Modules of C7 Bind to the C345C Domain of C51
TLDR
A model for an irreversible membrane attack complex assembly is suggested in which the C7 FIMs, but not those in C6, are bound to the C345C domain of C5 within the fully assembled complex. Expand
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TLDR
The membrane attack complex of complement is formed by the molecular fusion of the five terminal complement proteins, C5, C6, C7, C8, and C9, with the precursor C5b-8 complex. Expand
Identity of the Segment of Human Complement C8 Recognized by Complement Regulatory Protein CD59 (*)
TLDR
Functional evidence and functional evidence confirmed that CD59 recognizes a conformationally sensitive epitope that is within a segment of human C8α internal to residues 320-415, and suggest that optimal interaction of CD59 with this segment ofhuman C8β is influenced by N-terminal flanking sequence in C8 α and by human C7β, but is unaffected by C8. Expand
An indel within the C8 alpha subunit of human complement C8 mediates intracellular binding of C8 gamma and formation of C8 alpha-gamma.
TLDR
Results indicate (a) intracellular binding of C8gamma to C8alpha is mediated principally by residues contained within the C8 alpha indel, (b) binding is not strictly dependent on Cys(164), and (c) C8Gamma must contain a complementary binding site for the C 8alpha indel. Expand
The Four Terminal Components of the Complement System AreC-Mannosylated on Multiple Tryptophan Residues*
TLDR
The terminal components of the human complement system (C6, C7, C8, and C9), which contain multiple and complex recognition motifs, were examined and the results suggest further candidates for C-mannosylation. Expand
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