3SE3

human IFNa2-IFNAR ternary complex

Summary for 3SE3

• Entry DOI: 10.2210/pdb3se3/pdb
• Related: 3S8W 3S98 3S9D 3SE4
• Descriptor: Interferon alpha/beta receptor 1, Interferon alpha 2b, Interferon alpha/beta receptor 2, ... (4 entities in total)
• Functional Keywords: type i interferon signaling complex, extracellular space, immune system receptor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 90137.52

Authors

Thomas, C.,Garcia, K.C. (deposition date: 2011-06-10, release date: 2011-08-31, Last modification date: 2023-09-13)

Primary citation

Thomas, C.,Moraga, I.,Levin, D.,Krutzik, P.O.,Podoplelova, Y.,Trejo, A.,Lee, C.,Yarden, G.,Vleck, S.E.,Glenn, J.S.,Nolan, G.P.,Piehler, J.,Schreiber, G.,Garcia, K.C.
Structural linkage between ligand discrimination and receptor activation by type I interferons.
Cell(Cambridge,Mass.), 146:621-632, 2011

PubMed Abstract: Type I Interferons (IFNs) are important cytokines for innate immunity against viruses and cancer. Sixteen human type I IFN variants signal through the same cell-surface receptors, IFNAR1 and IFNAR2, yet they can evoke markedly different physiological effects. The crystal structures of two human type I IFN ternary signaling complexes containing IFNα2 and IFNω reveal recognition modes and heterotrimeric architectures that are unique among the cytokine receptor superfamily but conserved between different type I IFNs. Receptor-ligand cross-reactivity is enabled by conserved receptor-ligand "anchor points" interspersed among ligand-specific interactions that "tune" the relative IFN-binding affinities, in an apparent extracellular "ligand proofreading" mechanism that modulates biological activity. Functional differences between IFNs are linked to their respective receptor recognition chemistries, in concert with a ligand-induced conformational change in IFNAR1, that collectively control signal initiation and complex stability, ultimately regulating differential STAT phosphorylation profiles, receptor internalization rates, and downstream gene expression patterns.

PubMed: 21854986
DOI: 10.1016/j.cell.2011.06.048

Experimental method

X-RAY DIFFRACTION (4.0001 Å)