4Q7D

Wild type Fc (wtFc)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.211 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Structural characterization of anti-inflammatory immunoglobulin g fc proteins.

Ahmed, A.A.Giddens, J.Pincetic, A.Lomino, J.V.Ravetch, J.V.Wang, L.X.Bjorkman, P.J.

(2014) J Mol Biol 426: 3166-3179

  • DOI: 10.1016/j.jmb.2014.07.006
  • Primary Citation of Related Structures:  
    4Q6Y, 4Q74, 4Q7D

  • PubMed Abstract: 
  • Immunoglobulin G (IgG) is a central mediator of host defense due to its ability to recognize and eliminate pathogens. The recognition and effector responses are encoded on distinct regions of IgGs. The diversity of the antigen recognition Fab domains accounts for IgG's ability to bind with high specificity to essentially any antigen ...

    Immunoglobulin G (IgG) is a central mediator of host defense due to its ability to recognize and eliminate pathogens. The recognition and effector responses are encoded on distinct regions of IgGs. The diversity of the antigen recognition Fab domains accounts for IgG's ability to bind with high specificity to essentially any antigen. Recent studies have indicated that the Fc effector domain also displays considerable heterogeneity, accounting for its complex effector functions of inflammation, modulation, and immune suppression. Therapeutic anti-tumor antibodies, for example, require the pro-inflammatory properties of the IgG Fc to eliminate tumor cells, while the anti-inflammatory activity of intravenous IgG requires specific Fc glycans for activity. In particular, the anti-inflammatory activity of intravenous IgG is ascribed to a small population of IgGs in which the Asn297-linked complex N-glycans attached to each Fc CH2 domain include terminal α2,6-linked sialic acids. We used chemoenzymatic glycoengineering to prepare fully disialylated IgG Fc and solved its crystal structure. Comparison of the structures of asialylated Fc, sialylated Fc, and F241A Fc, a mutant that displays increased glycan sialylation, suggests that increased conformational flexibility of the CH2 domain is associated with the switch from pro-inflammatory to anti-inflammatory activity of the Fc.


    Organizational Affiliation

    Division of Biology and Biological Engineering 114-96, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA. Electronic address: bjorkman@caltech.edu.



Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
Ig gamma-1 chain C regionA, B221Homo sapiensMutation(s): 0 
Gene Names: IGHG1
UniProt & NIH Common Fund Data Resources
Find proteins for P01857 (Homo sapiens)
Explore P01857 
Go to UniProtKB:  P01857
PHAROS:  P01857
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01857
Protein Feature View
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  • Reference Sequence
Oligosaccharides

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Entity ID: 2
MoleculeChainsChain Length2D DiagramGlycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranoseC, D 8N-Glycosylation Oligosaccharides Interaction
Glycosylation Resources
GlyTouCan:  G80858MF
GlyCosmos:  G80858MF
GlyGen:  G80858MF
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.211 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.52α = 90
b = 79.48β = 90
c = 137.94γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report




Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-07-23
    Type: Initial release
  • Version 1.1: 2014-07-30
    Changes: Database references
  • Version 1.2: 2014-09-03
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary