Structural Insights Into the Neutralization Properties of a Human Anti-Interferon Monoclonal AntibodyStructural Insights Into the Neutralization Properties of a Human Anti-Interferon Monoclonal Antibody

Structural highlights

4ypg is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q6PJF2_HUMAN

Publication Abstract from PubMed

We report the three-dimensional structure of human interferon alpha-2A (IFN-alpha2A) bound to the Fab fragment of a therapeutic monoclonal antibody (sifalimumab; IgG1/k). The structure of the corresponding complex was solved at a resolution of 3.0 A using molecular replacement and constitutes the first reported structure of a human type I IFN bound to a therapeutic antibody. This study revealed the major contribution made by the first complementarity determining region (CDR) in each of sifalimumab light and heavy chains. These data also provided the molecular basis for sifalimumab mechanism of action. We propose that its interferon-neutralizing properties are the results of direct competition for IFN-alpha2A binding to the IFN receptor subunit 1 (IFNAR1) and do not involve inhibiting IFN-alpha2A binding to the IFN receptor subunit 2 (IFNAR2).

Structural Insights Into the Neutralization Properties of the Fully Human, Anti-Interferon Monoclonal Antibody Sifalimumab.,Oganesyan V, Peng L, Woods RM, Wu H, Dall'Acqua WF J Biol Chem. 2015 Apr 29. pii: jbc.M115.652156. PMID:25925951[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Oganesyan V, Peng L, Woods RM, Wu H, Dall'Acqua WF. Structural Insights Into the Neutralization Properties of the Fully Human, Anti-Interferon Monoclonal Antibody Sifalimumab. J Biol Chem. 2015 Apr 29. pii: jbc.M115.652156. PMID:25925951 doi:http://dx.doi.org/10.1074/jbc.M115.652156

4ypg, resolution 3.00Å

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