TYK2识别IFN受体的结构基础

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2014-04-02 DOI:10.2210/pdb4po6/pdb

H. Wallweber, C. Tam, Y. Franke, M. Starovasnik, P. Lupardus

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引用次数: 4

摘要

酪氨酸激酶2 (TYK2)是非受体酪氨酸激酶Janus kinase (JAK)家族的一员，在免疫反应和发育过程中对适当的信号传导至关重要。在这里，我们展示了2.0埃分辨率的人类TYK2受体结合片段的晶体结构，该片段包含FERM和SH2结构域，并与含有IFNα受体(IFNAR1)细胞内肽基元的所谓“box2”复合物。TYK2-IFNAR1界面揭示了一种意想不到的受体结合模式，它模拟了SH2结构域-磷酸肽的相互作用，谷氨酸取代了典型的磷酸酪氨酸残基。这种结构为我们了解JAK及其同源受体的复合体提供了第一个视角，并定义了JAK与不同受体序列相互作用的分子逻辑。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Structural basis of IFN receptor recognition by TYK2

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.

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来源期刊

Nature Structural &Molecular Biology 生物-生化与分子生物学

自引率

1.80%

发文量

160

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.