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The structural basis of the activation and inhibition of DSR2 NADase by phage proteins.
Wang, Ruiwen; Xu, Qi; Wu, Zhuoxi; Li, Jialu; Guo, Hao; Liao, Tianzhui; Shi, Yuan; Yuan, Ling; Gao, Haishan; Yang, Rong; Shi, Zhubing; Li, Faxiang.
Afiliación
  • Wang R; MOE Key Laboratory of Rare Pediatric Diseases, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
  • Xu Q; Zhejiang Key Laboratory of Structural Biology, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
  • Wu Z; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
  • Li J; MOE Key Laboratory of Rare Pediatric Diseases, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
  • Guo H; Zhejiang Key Laboratory of Structural Biology, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
  • Liao T; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
  • Shi Y; MOE Key Laboratory of Rare Pediatric Diseases, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
  • Yuan L; MOE Key Laboratory of Rare Pediatric Diseases, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
  • Gao H; Zhejiang Key Laboratory of Structural Biology, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
  • Yang R; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
  • Shi Z; MOE Key Laboratory of Rare Pediatric Diseases, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
  • Li F; Zhejiang Key Laboratory of Structural Biology, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Nat Commun ; 15(1): 6185, 2024 Jul 23.
Article en En | MEDLINE | ID: mdl-39039073
ABSTRACT
DSR2, a Sir2 domain-containing protein, protects bacteria from phage infection by hydrolyzing NAD+. The enzymatic activity of DSR2 is triggered by the SPR phage tail tube protein (TTP), while suppressed by the SPbeta phage-encoded DSAD1 protein, enabling phages to evade the host defense. However, the molecular mechanisms of activation and inhibition of DSR2 remain elusive. Here, we report the cryo-EM structures of apo DSR2, DSR2-TTP-NAD+ and DSR2-DSAD1 complexes. DSR2 assembles into a head-to-head tetramer mediated by its Sir2 domain. The C-terminal helical regions of DSR2 constitute four partner-binding cavities with opened and closed conformation. Two TTP molecules bind to two of the four C-terminal cavities, inducing conformational change of Sir2 domain to activate DSR2. Furthermore, DSAD1 competes with the activator for binding to the C-terminal cavity of DSR2, effectively suppressing its enzymatic activity. Our results provide the mechanistic insights into the DSR2-mediated anti-phage defense system and DSAD1-dependent phage immune evasion.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microscopía por Crioelectrón / NAD Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microscopía por Crioelectrón / NAD Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido