6XZ6

Structure of the trypanosome brucei factor H receptor bound to domain D5 of bovine factor H


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.195 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

A receptor for the complement regulator factor H increases transmission of trypanosomes to tsetse flies.

Macleod, O.J.S.Bart, J.M.MacGregor, P.Peacock, L.Savill, N.J.Hester, S.Ravel, S.Sunter, J.D.Trevor, C.Rust, S.Vaughan, T.J.Minter, R.Mohammed, S.Gibson, W.Taylor, M.C.Higgins, M.K.Carrington, M.

(2020) Nat Commun 11: 1326-1326

  • DOI: https://doi.org/10.1038/s41467-020-15125-y
  • Primary Citation of Related Structures:  
    6XZ6

  • PubMed Abstract: 

    Persistent pathogens have evolved to avoid elimination by the mammalian immune system including mechanisms to evade complement. Infections with African trypanosomes can persist for years and cause human and animal disease throughout sub-Saharan Africa. It is not known how trypanosomes limit the action of the alternative complement pathway. Here we identify an African trypanosome receptor for mammalian factor H, a negative regulator of the alternative pathway. Structural studies show how the receptor binds ligand, leaving inhibitory domains of factor H free to inactivate complement C3b deposited on the trypanosome surface. Receptor expression is highest in developmental stages transmitted to the tsetse fly vector and those exposed to blood meals in the tsetse gut. Receptor gene deletion reduced tsetse infection, identifying this receptor as a virulence factor for transmission. This demonstrates how a pathogen evolved a molecular mechanism to increase transmission to an insect vector by exploitation of a mammalian complement regulator.


  • Organizational Affiliation

    Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GARP domain-containing protein
A, C
229Trypanosoma brucei brucei TREU927Mutation(s): 0 
Gene Names: Tb927.5.4020
UniProt
Find proteins for Q57Z47 (Trypanosoma brucei brucei (strain 927/4 GUTat10.1))
Explore Q57Z47 
Go to UniProtKB:  Q57Z47
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ57Z47
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Complement factor H
B, D
61Bos taurusMutation(s): 0 
Gene Names: CFHHF1
UniProt
Find proteins for Q28085 (Bos taurus)
Explore Q28085 
Go to UniProtKB:  Q28085
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ28085
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.195 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 160.505α = 90
b = 66.056β = 94.44
c = 71.018γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Medical Research Council (MRC, United Kingdom)MR/P001424/1

Revision History  (Full details and data files)

  • Version 1.0: 2020-03-25
    Type: Initial release
  • Version 1.1: 2024-01-24
    Changes: Data collection, Database references, Refinement description