<br>cGLR 是先天免疫中一个多样化的模式识别受体家族,Cell

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cGLR 是先天免疫中一个多样化的模式识别受体家族
Cell ( IF 45.5 ) Pub Date : 2023-06-27 , DOI: 10.1016/j.cell.2023.05.038
Yao Li ₁ , Kailey M Slavik ₂ , Hunter C Toyoda ₂ , Benjamin R Morehouse ₂ , Carina C de Oliveira Mann ₃ , Anamaria Elek ₄ , Shani Levy ₄ , Zhenwei Wang ₅ , Kepler S Mears ₆ , Jingjing Liu ₆ , Dmitry Kashin ₇ , Ximing Guo ₅ , Tali Mass ₈ , Arnau Sebé-Pedrós ₉ , Frank Schwede ₇ , Philip J Kranzusch ₁

Affiliation

Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Parker Institute for Cancer Immunotherapy at Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Institute of Virology, Technical University of Munich, 81675 Munich, Germany.
Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Haskin Shellfish Research Laboratory, Department of Marine and Coastal Sciences, Rutgers University, Port Norris, NJ 08349, USA.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Biolog Life Science Institute GmbH & Co. KG, Flughafendamm 9a, 28199 Bremen, Germany.
Department of Marine Biology, The Leon H. Charney School of Marine Sciences, University of Haifa, Mt. Carmel, Haifa 3498838, Israel; Morris Kahn Marine Research Station, The Leon H. Charney School of Marine Sciences, University of Haifa, Sdot Yam, Israel.
Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; ICREA, Barcelona, Spain.

环 GMP-AMP 合酶 (cGAS) 是人体细胞中的一种酶，控制对胞质 DNA 的免疫反应。结合 DNA 后，cGAS 合成核苷酸信号 2'3'-cGAMP，激活 STING 依赖性下游免疫。在这里，我们发现 cGAS 样受体 (cGLR) 构成先天免疫中模式识别受体的主要家族。基于最近的分析，我们确定了几乎所有后生动物门中都存在超过 3,000 个 cGLR。对 150 种动物 cGLR 进行的正向生化筛选揭示了保守的信号传导机制，包括对 dsDNA 和 dsRNA 配体的响应以及核苷酸信号 cGAMP、c-UMP-AMP 和 c-di-AMP 异构体的合成。结合珊瑚和牡蛎动物的结构生物学和分析，我们解释了不同核苷酸信号的合成如何使细胞能够控制离散的 cGLR-STING 信号通路。我们的结果揭示了 cGLR 作为一个广泛存在的模式识别受体家族，并建立了控制动物免疫中核苷酸信号传导的分子规则。

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更新日期：2023-06-27

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