4Z5R

Rontalizumab Fab bound to Interferon-a2

Summary for 4Z5R

• Entry DOI: 10.2210/pdb4z5r/pdb
• Descriptor: Interferon alpha-2, anti-IFN-a antibody rontalizumab light chain, anti-IFN-a antibody rontalizumab heavy chain modules VH and CH1 (Fab), ... (4 entities in total)
• Functional Keywords: antibody, interferon, cytokine-immune system complex, cytokine/immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted: P01563
• Total number of polymer chains: 24
• Total formula weight: 540246.16

Authors

Eigenbrot, C.,Maurer, B.,Bosanac, I. (deposition date: 2015-04-02, release date: 2015-07-08, Last modification date: 2024-10-09)

Primary citation

Maurer, B.,Bosanac, I.,Shia, S.,Kwong, M.,Corpuz, R.,Vandlen, R.,Schmidt, K.,Eigenbrot, C.
Structural basis of the broadly neutralizing anti-interferon-alpha antibody rontalizumab.
Protein Sci., 24:1440-1450, 2015

PubMed Abstract: Interferons-alpha (IFN-α) 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-β, IFN-κ and IFN-ω have sequences 29-33%, 29-32% and 56-60% similar to the IFN-αs, 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-α has been used to treat infection by hepatitis-virus type C (HCV) and a correlation between hyperactivity of IFN-α-induced signaling and systemic lupus erythematosis (SLE), or lupus, has been noted. Anti-IFN-α 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-α2 at 3Å resolution and find substantial overlap of the antibody and IFNA2 epitopes on IFN-α2.

PubMed: 26099203
DOI: 10.1002/pro.2729

Experimental method

X-RAY DIFFRACTION (3 Å)