Crystal structure of the MACPF domain of human complement protein C8 alpha in complex with the C8 gamma subunit.

@article{Slade2008CrystalSO,
  title={Crystal structure of the MACPF domain of human complement protein C8 alpha in complex with the C8 gamma subunit.},
  author={D. J. Slade and L. Lovelace and M. Chruszcz and W. Minor and L. Lebioda and J. Sodetz},
  journal={Journal of molecular biology},
  year={2008},
  volume={379 2},
  pages={
          331-42
        }
}
Human C8 is one of five complement components (C5b, C6, C7, C8, and C9) that assemble on bacterial membranes to form a porelike structure referred to as the "membrane attack complex" (MAC). C8 contains three genetically distinct subunits (C8 alpha, C8 beta, C8 gamma) arranged as a disulfide-linked C8 alpha-gamma dimer that is noncovalently associated with C8 beta. C6, C7 C8 alpha, C8 beta, and C9 are homologous. All contain N- and C-terminal modules and an intervening 40-kDa segment referred to… Expand
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TLDR
This is the first structure of a MAC family member and of a human MACPF-containing protein, and shows the modules in C8α and C8β are located on the periphery of C8 and not likely to interact with the target membrane, leading to a model of the MAC that explains how C8-C9 and C9-C 9 interactions could facilitate refolding and insertion of putative MACPF transmembrane β-hairpins to form a circular pore. Expand
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Crystal structure of complement protein C8γ in complex with a peptide containing the C8γ binding site on C8α: Implications for C8γ ligand binding☆
TLDR
In the present study, C8γ containing a C40A substitution was co-crystallized with a synthetic indel peptide containing the equivalent of a C8α C164A substitution, suggesting a role for C8 α in regulating access to the putative C8β ligand binding site. 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
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
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
Structural features of the ligand binding site on human complement protein C8gamma: a member of the lipocalin family.
TLDR
Binding experiments performed using lauric acid as a pseudoligand indicate that the lower cavity in C8gamma could accommodate a ligand if such a ligands has a narrow hydrophobic moiety at one end. Expand
Role of the human C8 subunits in complement-mediated bacterial killing: evidence that C8 gamma is not essential.
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
Expression and Characterization of Recombinant Subunits of Human Complement Component C8: Further Analysis of the Function of C8α and C8γ
TLDR
The results indicate that the biosynthesis and secretion of C8α-γ is not dependent on C8β, which is consistent with in vivo observations in C8 β-deficient humans and C8γ does not bind retinol; therefore, it cannot function as aretinol transport protein. 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
Functional domains of the alpha subunit of the eighth component of human complement: identification and characterization of a distinct binding site for the gamma chain.
The purified gamma subunit of the eighth component of human complement (C8) was used to characterize its site of interaction within C8 and to probe the ultrastructure of membrane-bound C5b-8 andExpand
Structure of the human C7 gene and comparison with the C6, C8A, C8B, and C9 genes.
TLDR
It is shown here that the C7 gene is highly homologous to that for C6, and also to C8A, C8B, and C9, confirming and extending the published data. Expand
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