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Viral DNA Binding to NLRC3, an Inhibitory Nucleic Acid Sensor, Unleashes STING, a Cyclic Dinucleotide Receptor that Activates Type I Interferon.
Li, Xin; Deng, Meng; Petrucelli, Alex S; Zhu, Cheng; Mo, Jinyao; Zhang, Lu; Tam, Jason W; Ariel, Pablo; Zhao, Baoyu; Zhang, Song; Ke, Hengming; Li, Pingwei; Dokholyan, Nikolay V; Duncan, Joseph A; Ting, Jenny P-Y.
Afiliación
  • Li X; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Deng M; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Oral and Craniofacial Biomedicine PhD Program, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Petrucelli AS; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Zhu C; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Mo J; Department of Medicine, Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Zhang L; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Sarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA.
  • Tam JW; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Ariel P; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Zhao B; Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
  • Zhang S; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Ke H; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Li P; Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
  • Dokholyan NV; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA; Departments of Pharmacology and Biochemistry and Molecular Biology, Penn State College
  • Duncan JA; Department of Medicine, Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Ting JP; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: jenny_ting@med.unc.edu.
Immunity ; 50(3): 591-599.e6, 2019 03 19.
Article en En | MEDLINE | ID: mdl-30893587
Immune suppression is a crucial component of immunoregulation and a subgroup of nucleotide-binding domain (NBD), leucine-rich repeat (LRR)-containing proteins (NLRs) attenuate innate immunity. How this inhibitory function is controlled is unknown. A key question is whether microbial ligands can regulate this inhibition. NLRC3 is a negative regulator that attenuates type I interferon (IFN-I) response by sequestering and attenuating stimulator of interferon genes (STING) activation. Here, we report that NLRC3 binds viral DNA and other nucleic acids through its LRR domain. DNA binding to NLRC3 increases its ATPase activity, and ATP-binding by NLRC3 diminishes its interaction with STING, thus licensing an IFN-I response. This work uncovers a mechanism wherein viral nucleic acid binding releases an inhibitory innate receptor from its target.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN Viral / Interferón Tipo I / Péptidos y Proteínas de Señalización Intercelular / Proteínas de la Membrana Límite: Animals / Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN Viral / Interferón Tipo I / Péptidos y Proteínas de Señalización Intercelular / Proteínas de la Membrana Límite: Animals / Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos