4YPG

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

Summary for 4YPG

• Entry DOI: 10.2210/pdb4ypg/pdb
• Descriptor: Sifalimumab light chain, Sifalimumab heavy chain, Interferon alpha-2, ... (5 entities in total)
• Functional Keywords: therapeutic mab, ifn-alpha2a, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 131149.01

Authors

Oganesyan, V.,Dall'Acqua, W.F. (deposition date: 2015-03-12, release date: 2015-05-06, Last modification date: 2024-10-23)

Primary citation

Oganesyan, V.,Peng, L.,Woods, R.M.,Wu, H.,Dall'Acqua, W.F.
Structural Insights into the Neutralization Properties of the Fully Human, Anti-interferon Monoclonal Antibody Sifalimumab.
J.Biol.Chem., 290:14979-14985, 2015

PubMed Abstract: We report the three-dimensional structure of human interferon α-2A (IFN-α2A) bound to the Fab fragment of a therapeutic monoclonal antibody (sifalimumab; IgG1/κ). The structure of the corresponding complex was solved at a resolution of 3.0 Å 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 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 result of direct competition for IFN-α2A binding to the IFN receptor subunit 1 (IFNAR1) and do not involve inhibiting IFN-α2A binding to the IFN receptor subunit 2 (IFNAR2).

PubMed: 25925951
DOI: 10.1074/jbc.M115.652156

Experimental method

X-RAY DIFFRACTION (3 Å)