6S08

Crystal Structure of Properdin (TSR domains N1 & 456)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.03 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.214 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 3.1 of the entry. See complete history


Literature

Insights Into Enhanced Complement Activation by Structures of Properdin and Its Complex With the C-Terminal Domain of C3b.

van den Bos, R.M.Pearce, N.M.Granneman, J.Brondijk, T.H.C.Gros, P.

(2019) Front Immunol 10: 2097-2097

  • DOI: https://doi.org/10.3389/fimmu.2019.02097
  • Primary Citation of Related Structures:  
    6S08, 6S0A, 6S0B

  • PubMed Abstract: 

    Properdin enhances complement-mediated opsonization of targeted cells and particles for immune clearance. Properdin occurs as dimers, trimers and tetramers in human plasma, which recognize C3b-deposited surfaces, promote formation, and prolong the lifetime of C3bBb-enzyme complexes that convert C3 into C3b, thereby enhancing the complement-amplification loop. Here, we report crystal structures of monomerized properdin, which was produced by co-expression of separate N- and C-terminal constructs that yielded monomer-sized properdin complexes that stabilized C3bBb. Consistent with previous low-resolution X-ray and EM data, the crystal structures revealed ring-shaped arrangements that are formed by interactions between thrombospondin type-I repeat (TSR) domains 4 and 6 of one protomer interacting with the N-terminal domain (which adopts a short transforming-growth factor B binding protein-like fold) and domain TSR1 of a second protomer, respectively. Next, a structure of monomerized properdin in complex with the C-terminal domain of C3b showed that properdin-domain TSR5 binds along the C-terminal α-helix of C3b, while two loops, one from domain TSR5 and one from TSR6, extend and fold around the C3b C-terminus like stirrups. This suggests a mechanistic model in which these TSR5 and TSR6 "stirrups" bridge interactions between C3b and factor B or its fragment Bb, and thereby enhance formation of C3bB pro-convertases and stabilize C3bBb convertases. In addition, properdin TSR6 would sterically block binding of the protease factor I to C3b, thus limiting C3b proteolytic degradation. The presence of a valine instead of a third tryptophan in the canonical Trp-ladder of TSR domains in TSR4 allows a remarkable ca. 60°-domain bending motion of TSR4. Together with variable positioning of TSR2 and, putatively, TSR3, this explains the conformational flexibility required for properdin to form dimers, trimers, and tetramers. In conclusion, the results indicate that binding avidity of oligomeric properdin is needed to distinguish surface-deposited C3b molecules from soluble C3b or C3 and suggest that properdin-mediated interactions bridging C3b-B and C3b-Bb enhance affinity, thus promoting convertase formation and stabilization. These mechanisms explain the enhancement of complement-mediated opsonization of targeted cells and particle for immune clearance.


  • Organizational Affiliation

    Crystal and Structural Chemistry, Department of Chemistry, Faculty of Science, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, Netherlands.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Properdin225Homo sapiensMutation(s): 0 
Gene Names: CFPPFC
UniProt & NIH Common Fund Data Resources
Find proteins for P27918 (Homo sapiens)
Explore P27918 
Go to UniProtKB:  P27918
PHAROS:  P27918
GTEx:  ENSG00000126759 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP27918
Glycosylation
Glycosylation Sites: 8Go to GlyGen: P27918-1
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Properdin110Homo sapiensMutation(s): 0 
Gene Names: CFPPFC
UniProt & NIH Common Fund Data Resources
Find proteins for P27918 (Homo sapiens)
Explore P27918 
Go to UniProtKB:  P27918
PHAROS:  P27918
GTEx:  ENSG00000126759 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP27918
Glycosylation
Glycosylation Sites: 2Go to GlyGen: P27918-1
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-glucopyranose-(1-3)-alpha-L-fucopyranose
C
2O-Glycosylation
Glycosylation Resources
GlyTouCan:  G36855WW
GlyCosmos:  G36855WW
GlyGen:  G36855WW
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MAN
Query on MAN

Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
G [auth A]
H [auth A]
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
K [auth A],
M [auth B]
alpha-D-mannopyranose
C6 H12 O6
WQZGKKKJIJFFOK-PQMKYFCFSA-N
FUC
Query on FUC

Download Ideal Coordinates CCD File 
N [auth B]alpha-L-fucopyranose
C6 H12 O5
SHZGCJCMOBCMKK-SXUWKVJYSA-N
PGE
Query on PGE

Download Ideal Coordinates CCD File 
J [auth A]TRIETHYLENE GLYCOL
C6 H14 O4
ZIBGPFATKBEMQZ-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
L [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.03 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.214 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 111.995α = 90
b = 114.86β = 99.56
c = 39.822γ = 90
Software Package:
Software NamePurpose
DIALSdata reduction
STARANISOdata scaling
PHASERphasing
Cootmodel building
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Dutch Kidney FoundationNetherlands13OCA27

Revision History  (Full details and data files)

  • Version 1.0: 2019-09-04
    Type: Initial release
  • Version 1.1: 2019-10-02
    Changes: Data collection, Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
  • Version 3.0: 2024-07-24
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Structure summary
  • Version 3.1: 2024-11-20
    Changes: Structure summary