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|3s9d, resolution 2.00Å ()|
|Gene:||IFNA2 (Homo sapiens), IFNAR2, IFNABR, IFNARB (Homo sapiens)|
binary complex between IFNa2 and IFNAR2
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 IFNalpha2 and IFNomega 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.
Structural linkage between ligand discrimination and receptor activation by type I interferons., Thomas C, Moraga I, Levin D, Krutzik PO, Podoplelova Y, Trejo A, Lee C, Yarden G, Vleck SE, Glenn JS, Nolan GP, Piehler J, Schreiber G, Garcia KC, Cell. 2011 Aug 19;146(4):621-32. PMID:21854986
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Thomas C, Moraga I, Levin D, Krutzik PO, Podoplelova Y, Trejo A, Lee C, Yarden G, Vleck SE, Glenn JS, Nolan GP, Piehler J, Schreiber G, Garcia KC. Structural Linkage between Ligand Discrimination and Receptor Activation by Type I Interferons. Cell. 2011 Aug 19;146(4):621-32. PMID:21854986 doi:10.1016/j.cell.2011.06.048