4z5r
Rontalizumab Fab bound to Interferon-a2
Structural highlights
FunctionIFNA2_HUMAN Produced by macrophages, IFN-alpha have antiviral activities. Publication Abstract from PubMedInterferons-alpha (IFN-alpha) 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-beta, IFN-kappa and IFN-omega have sequences 29-33%, 29-32% and 56-60% similar to the IFN-alphas, 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-alpha has been used to treat infection by hepatitis-virus type C (HCV) and a correlation between hyperactivity of IFN-alpha -induced signaling and systemic lupus erythematosis (SLE), or lupus, has been noted. Anti-IFN-alpha 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-alpha2 at 3A resolution and find substantial overlap of the antibody and IFNA2 epitopes on IFN-alpha2. This article is protected by copyright. All rights reserved. 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 Protein Sci. 2015 Jun 22. doi: 10.1002/pro.2729. PMID:26099203[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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