4N0F

Human FcRn complexed with human serum albumin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.02 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural Insights into Neonatal Fc Receptor-based Recycling Mechanisms.

Oganesyan, V.Damschroder, M.M.Cook, K.E.Li, Q.Gao, C.Wu, H.Dall'acqua, W.F.

(2014) J Biol Chem 289: 7812-7824

  • DOI: https://doi.org/10.1074/jbc.M113.537563
  • Primary Citation of Related Structures:  
    4N0F, 4N0U

  • PubMed Abstract: 

    We report the three-dimensional structure of human neonatal Fc receptor (FcRn) bound concurrently to its two known ligands. More particularly, we solved the crystal structure of the complex between human FcRn, wild-type human serum albumin (HSA), and a human Fc engineered for improved pharmacokinetics properties (Fc-YTE). The crystal structure of human FcRn bound to wild-type HSA alone is also presented. HSA domain III exhibits an extensive interface of contact with FcRn, whereas domain I plays a lesser role. A molecular explanation for the HSA recycling mechanism is provided with the identification of FcRn His(161) as the only potential direct contributor to the corresponding pH-dependent process. At last, this study also allows an accurate structural definition of residues considered for decades as important to the human IgG/FcRn interaction and reveals Fc His(310) as a significant contributor to pH-dependent binding. Finally, we explain various structural mechanisms by which several Fc mutations (including YTE) result in increased human IgG binding to FcRn. Our study provides an unprecedented relevant understanding of the molecular basis of human Fc interaction with human FcRn.


  • Organizational Affiliation

    From the Department of Antibody Discovery and Protein Engineering, MedImmune, Gaithersburg, Maryland 20878.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
IgG receptor FcRn large subunit p51A,
D [auth E],
G [auth H],
J [auth K]
271Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P55899 (Homo sapiens)
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Go to UniProtKB:  P55899
PHAROS:  P55899
GTEx:  ENSG00000104870 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP55899
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulinB,
E [auth F],
H [auth I],
K [auth L]
99Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P61769 (Homo sapiens)
Explore P61769 
Go to UniProtKB:  P61769
PHAROS:  P61769
GTEx:  ENSG00000166710 
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UniProt GroupP61769
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Serum albuminC [auth D],
F [auth G],
I [auth J],
L [auth M]
585Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P02768 (Homo sapiens)
Explore P02768 
Go to UniProtKB:  P02768
PHAROS:  P02768
GTEx:  ENSG00000163631 
Entity Groups  
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UniProt GroupP02768
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.02 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.225 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 136.469α = 90
b = 115.925β = 104.47
c = 186.237γ = 90
Software Package:
Software NamePurpose
PROTEUM PLUSdata collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-02-05
    Type: Initial release
  • Version 1.1: 2014-04-02
    Changes: Database references
  • Version 1.2: 2014-04-09
    Changes: Other