H. Wallweber, C. Tam, Y. Franke, M. Starovasnik, P. Lupardus
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引用次数: 4
Abstract
Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family of non-receptor tyrosine kinases, which are essential for proper signaling in immune responses and development. Here we present a 2.0 angstrom resolution crystal structure of a receptor-binding fragment of human TYK2 encompassing the FERM and SH2 domains in complex with a so-called “box2” containing intracellular peptide motif from the IFNα receptor (IFNAR1). The TYK2–IFNAR1 interface reveals an unexpected receptor-binding mode that mimics a SH2 domain–phosphopeptide interaction, with a glutamate replacing the canonical phosphotyrosine residue. This structure provides the first view to our knowledge of a JAK in complex with its cognate receptor and defines the molecular logic through which JAKs evolved to interact with divergent receptor sequences.
期刊介绍：
Nature Structural & Molecular Biology is a monthly journal that focuses on the functional and mechanistic understanding of how molecular components in a biological process work together. It serves as an integrated forum for structural and molecular studies. The journal places a strong emphasis on the functional and mechanistic understanding of how molecular components in a biological process work together. Some specific areas of interest include the structure and function of proteins, nucleic acids, and other macromolecules, DNA replication, repair and recombination, transcription, regulation of transcription and translation, protein folding, processing and degradation, signal transduction, and intracellular signaling.
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