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Structural Insights into mitochondrial antiviral signaling protein (MAVS)-tumor necrosis factor receptor-associated factor 6 (TRAF6) signaling.
Shi, Zhubing; Zhang, Zhen; Zhang, Zhenzhen; Wang, Yanyan; Li, Chuanchuan; Wang, Xin; He, Feng; Sun, Lina; Jiao, Shi; Shi, Weiyang; Zhou, Zhaocai.
Afiliação
  • Shi Z; From the School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China, the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, State Key Laboratory of Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 20
  • Zhang Z; the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, State Key Laboratory of Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China, and.
  • Zhang Z; the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, State Key Laboratory of Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China, and.
  • Wang Y; the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, State Key Laboratory of Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China, and.
  • Li C; the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, State Key Laboratory of Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China, and.
  • Wang X; the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, State Key Laboratory of Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China, and.
  • He F; the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, State Key Laboratory of Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China, and.
  • Sun L; Qingdao Binhai University, Qingdao, Shandong 266555, China.
  • Jiao S; the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, State Key Laboratory of Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China, and.
  • Shi W; From the School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China, wshi@tongji.edu.cn.
  • Zhou Z; the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, State Key Laboratory of Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China, and zczhou@sibcb.ac.cn.
J Biol Chem ; 290(44): 26811-20, 2015 Oct 30.
Article em En | MEDLINE | ID: mdl-26385923
In response to viral infection, cytosolic retinoic acid-inducible gene I-like receptors sense viral RNA and promote oligomerization of mitochondrial antiviral signaling protein (MAVS), which then recruits tumor necrosis factor receptor-associated factor (TRAF) family proteins, including TRAF6, to activate an antiviral response. Currently, the interaction between MAVS and TRAF6 is only partially understood, and atomic details are lacking. Here, we demonstrated that MAVS directly interacts with TRAF6 through its potential TRAF6-binding motif 2 (T6BM2; amino acids 455-460). Further, we solved the crystal structure of MAVS T6BM2 in complex with the TRAF6 TRAF_C domain at 2.95 Å resolution. T6BM2 of MAVS binds to the canonical adaptor-binding groove of the TRAF_C domain. Structure-directed mutational analyses in vitro and in cells revealed that MAVS binding to TRAF6 via T6BM2 instead of T6BM1 is essential but not sufficient for an optimal antiviral response. Particularly, a MAVS mutant Y460E retained its TRAF6-binding ability as predicted but showed significantly impaired signaling activity, highlighting the functional importance of this tyrosine. Moreover, these observations were further confirmed in MAVS(-/-) mouse embryonic fibroblast cells. Collectively, our work provides a structural basis for understanding the MAVS-TRAF6 antiviral response.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Recombinantes de Fusão / Proteínas Adaptadoras de Transdução de Sinal / Fator 6 Associado a Receptor de TNF / Interações Hospedeiro-Patógeno / Fibroblastos / Mitocôndrias Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Recombinantes de Fusão / Proteínas Adaptadoras de Transdução de Sinal / Fator 6 Associado a Receptor de TNF / Interações Hospedeiro-Patógeno / Fibroblastos / Mitocôndrias Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article