3OJY

Crystal Structure of Human Complement Component C8


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.51 Å
  • R-Value Free: 0.337 
  • R-Value Work: 0.249 
  • R-Value Observed: 0.253 

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This is version 1.6 of the entry. See complete history


Literature

Structure of human C8 protein provides mechanistic insight into membrane pore formation by complement.

Lovelace, L.L.Cooper, C.L.Sodetz, J.M.Lebioda, L.

(2011) J Biol Chem 286: 17585-17592

  • DOI: https://doi.org/10.1074/jbc.M111.219766
  • Primary Citation of Related Structures:  
    2RD7, 3OJY

  • PubMed Abstract: 

    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) domain that has a key role in forming the MAC pore. Here, we report the 2.5 Å resolution crystal structure of human C8 purified from blood. This is the first structure of a MAC family member and of a human MACPF-containing protein. The structure shows the modules in C8α and C8β are located on the periphery of C8 and not likely to interact with the target membrane. The C8γ subunit, a member of the lipocalin family of proteins that bind and transport small lipophilic molecules, shows no occupancy of its putative ligand-binding site. C8α and C8β are related by a rotation of ∼22° with only a small translational component along the rotation axis. Evolutionary arguments suggest the geometry of binding between these two subunits is similar to the arrangement of C9 molecules within the MAC pore. This leads to a model of the MAC that explains how C8-C9 and C9-C9 interactions could facilitate refolding and insertion of putative MACPF transmembrane β-hairpins to form a circular pore.


  • Organizational Affiliation

    Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Complement component C8 alpha chain554Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P07357 (Homo sapiens)
Explore P07357 
Go to UniProtKB:  P07357
PHAROS:  P07357
GTEx:  ENSG00000157131 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07357
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Complement component C8 beta chain537Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P07358 (Homo sapiens)
Explore P07358 
Go to UniProtKB:  P07358
PHAROS:  P07358
GTEx:  ENSG00000021852 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07358
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Complement component C8 gamma chain182Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P07360 (Homo sapiens)
Explore P07360 
Go to UniProtKB:  P07360
PHAROS:  P07360
GTEx:  ENSG00000176919 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07360
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BMA
Query on BMA

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
H [auth A]
J [auth B]
E [auth A],
F [auth A],
G [auth A],
H [auth A],
J [auth B],
K [auth B],
L [auth B],
M [auth B]
beta-D-mannopyranose
C6 H12 O6
WQZGKKKJIJFFOK-RWOPYEJCSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
D [auth A],
I [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
TPO
Query on TPO
B
L-PEPTIDE LINKINGC4 H10 N O6 PTHR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.51 Å
  • R-Value Free: 0.337 
  • R-Value Work: 0.249 
  • R-Value Observed: 0.253 
  • Space Group: P 63
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 139.575α = 90
b = 139.575β = 90
c = 127.16γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
SERGUIdata collection
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-13
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-10-26
    Changes: Database references
  • Version 1.3: 2014-04-16
    Changes: Other
  • Version 1.4: 2017-11-08
    Changes: Refinement description
  • Version 1.5: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.6: 2023-09-06
    Changes: Data collection, Database references, Refinement description, Structure summary