4Z5R

Rontalizumab Fab bound to Interferon-a2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural basis of the broadly neutralizing anti-interferon-alpha antibody rontalizumab.

Maurer, B.Bosanac, I.Shia, S.Kwong, M.Corpuz, R.Vandlen, R.Schmidt, K.Eigenbrot, C.

(2015) Protein Sci 24: 1440-1450

  • DOI: https://doi.org/10.1002/pro.2729
  • Primary Citation of Related Structures:  
    4Z5R

  • PubMed Abstract: 

    Interferons-alpha (IFN-α) are the expressed gene products comprising thirteen type I interferons with protein pairwise sequence similarities in the 77-96% range. Three other widely expressed human type I interferons, IFN-β, IFN-κ and IFN-ω have sequences 29-33%, 29-32% and 56-60% similar to the IFN-αs, respectively. Type I interferons act on immune cells by producing subtly different immune-modulatory effects upon binding to the extracellular domains of a heterodimeric cell-surface receptor composed of IFNAR1 and IFNAR2, most notably anti-viral effects. IFN-α has been used to treat infection by hepatitis-virus type C (HCV) and a correlation between hyperactivity of IFN-α-induced signaling and systemic lupus erythematosis (SLE), or lupus, has been noted. Anti-IFN-α antibodies including rontalizumab have been under clinical study for the treatment of lupus. To better understand the rontalizumab mechanism of action and specificity, we determined the X-ray crystal structure of the Fab fragment of rontalizumab bound to human IFN-α2 at 3Å resolution and find substantial overlap of the antibody and IFNA2 epitopes on IFN-α2.


  • Organizational Affiliation

    Department of Structural Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California, 94080.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Interferon alpha-2165Homo sapiensMutation(s): 0 
Gene Names: IFNA2IFNA2AIFNA2BIFNA2C
UniProt & NIH Common Fund Data Resources
Find proteins for P01563 (Homo sapiens)
Explore P01563 
Go to UniProtKB:  P01563
PHAROS:  P01563
GTEx:  ENSG00000188379 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01563
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
anti-IFN-a antibody rontalizumab light chain218Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
anti-IFN-a antibody rontalizumab heavy chain modules VH and CH1 (Fab)225Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.223 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 90.829α = 90
b = 331.864β = 111.28
c = 98.142γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-07-08
    Type: Initial release
  • Version 1.1: 2015-09-09
    Changes: Database references
  • Version 1.2: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description