IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48291-4.html
   My bibliography  Save this article

Molecular basis of bacterial DSR2 anti-phage defense and viral immune evasion

Author

Listed:
  • Jiafeng Huang

    (Beijing Institute of Technology
    Chinese Academy of Sciences)

  • Keli Zhu

    (Beijing Institute of Technology)

  • Yina Gao

    (Chinese Academy of Sciences)

  • Feng Ye

    (Beijing Institute of Technology)

  • Zhaolong Li

    (Chinese Academy of Sciences)

  • Yao Ge

    (Beijing Institute of Technology)

  • Songqing Liu

    (Chinese Academy of Sciences)

  • Jing Yang

    (Peking University Aerospace School of Clinical Medicine)

  • Ang Gao

    (Beijing Institute of Technology
    Shandong First Medical University & Shandong Academy of Medical Sciences)

Abstract

Defense-associated sirtuin 2 (DSR2) systems are widely distributed across prokaryotic genomes, providing robust protection against phage infection. DSR2 recognizes phage tail tube proteins and induces abortive infection by depleting intracellular NAD+, a process that is counteracted by another phage-encoded protein, DSR Anti Defense 1 (DSAD1). Here, we present cryo-EM structures of Bacillus subtilis DSR2 in its apo, Tube-bound, and DSAD1-bound states. DSR2 assembles into an elongated tetramer, with four NADase catalytic modules clustered in the center and the regulatory-sensing modules distributed at four distal corners. Interestingly, monomeric Tube protein, rather than its oligomeric states, docks at each corner of the DSR2 tetramer to form a 4:4 DSR2-Tube assembly, which is essential for DSR2 NADase activity. DSAD1 competes with Tube for binding to DSR2 by occupying an overlapping region, thereby inhibiting DSR2 immunity. Thus, our results provide important insights into the assembly, activation and inhibition of the DSR2 anti-phage defense system.

Suggested Citation

  • Jiafeng Huang & Keli Zhu & Yina Gao & Feng Ye & Zhaolong Li & Yao Ge & Songqing Liu & Jing Yang & Ang Gao, 2024. "Molecular basis of bacterial DSR2 anti-phage defense and viral immune evasion," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48291-4
    DOI: 10.1038/s41467-024-48291-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48291-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-48291-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Tong Zhang & Hedvig Tamman & Kyo Coppieters ’t Wallant & Tatsuaki Kurata & Michele LeRoux & Sriram Srikant & Tetiana Brodiazhenko & Albinas Cepauskas & Ariel Talavera & Chloe Martens & Gemma C. Atkins, 2022. "Direct activation of a bacterial innate immune system by a viral capsid protein," Nature, Nature, vol. 612(7938), pages 132-140, December.
    3. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    4. Benjamin R. Morehouse & Apurva A. Govande & Adi Millman & Alexander F. A. Keszei & Brianna Lowey & Gal Ofir & Sichen Shao & Rotem Sorek & Philip J. Kranzusch, 2020. "STING cyclic dinucleotide sensing originated in bacteria," Nature, Nature, vol. 586(7829), pages 429-433, October.
    5. Donghyun Ka & Hyejin Oh & Eunyoung Park & Jeong-Han Kim & Euiyoung Bae, 2020. "Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NAD+ degradation," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    6. Zhangfei Shen & Xiao-Yuan Yang & Shiyu Xia & Wei Huang & Derek J. Taylor & Kotaro Nakanishi & Tian-Min Fu, 2023. "Oligomerization-mediated activation of a short prokaryotic Argonaute," Nature, Nature, vol. 621(7977), pages 154-161, September.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Ruiwen Wang & Qi Xu & Zhuoxi Wu & Jialu Li & Hao Guo & Tianzhui Liao & Yuan Shi & Ling Yuan & Haishan Gao & Rong Yang & Zhubing Shi & Faxiang Li, 2024. "The structural basis of the activation and inhibition of DSR2 NADase by phage proteins," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Hang Yin & Xuzichao Li & Xiaoshen Wang & Chendi Zhang & Jiaqi Gao & Guimei Yu & Qiuqiu He & Jie Yang & Xiang Liu & Yong Wei & Zhuang Li & Heng Zhang, 2024. "Insights into the modulation of bacterial NADase activity by phage proteins," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Ruiwen Wang & Qi Xu & Zhuoxi Wu & Jialu Li & Hao Guo & Tianzhui Liao & Yuan Shi & Ling Yuan & Haishan Gao & Rong Yang & Zhubing Shi & Faxiang Li, 2024. "The structural basis of the activation and inhibition of DSR2 NADase by phage proteins," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Xinmi Song & Sheng Lei & Shunhang Liu & Yanqiu Liu & Pan Fu & Zhifeng Zeng & Ke Yang & Yu Chen & Ming Li & Qunxin She & Wenyuan Han, 2023. "Catalytically inactive long prokaryotic Argonaute systems employ distinct effectors to confer immunity via abortive infection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Jun-Tao Zhang & Xiao-Yu Liu & Zhuolin Li & Xin-Yang Wei & Xin-Yi Song & Ning Cui & Jirui Zhong & Hongchun Li & Ning Jia, 2024. "Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Pierre Azoulay & Joshua Krieger & Abhishek Nagaraj, 2024. "Old Moats for New Models: Openness, Control, and Competition in Generative AI," NBER Chapters, in: Entrepreneurship and Innovation Policy and the Economy, volume 4, National Bureau of Economic Research, Inc.
    6. Deyun Qiu & Jinxin V. Pei & James E. O. Rosling & Vandana Thathy & Dongdi Li & Yi Xue & John D. Tanner & Jocelyn Sietsma Penington & Yi Tong Vincent Aw & Jessica Yi Han Aw & Guoyue Xu & Abhai K. Tripa, 2022. "A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    7. Shuo-Shuo Liu & Tian-Xia Jiang & Fan Bu & Ji-Lan Zhao & Guang-Fei Wang & Guo-Heng Yang & Jie-Yan Kong & Yun-Fan Qie & Pei Wen & Li-Bin Fan & Ning-Ning Li & Ning Gao & Xiao-Bo Qiu, 2024. "Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    8. Xiaoke Yang & Mingqi Zhu & Xue Lu & Yuxin Wang & Junyu Xiao, 2024. "Architecture and activation of human muscle phosphorylase kinase," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Efren Garcia-Maldonado & Andrew D. Huber & Sergio C. Chai & Stanley Nithianantham & Yongtao Li & Jing Wu & Shyaron Poudel & Darcie J. Miller & Jayaraman Seetharaman & Taosheng Chen, 2024. "Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    10. Kristy Rochon & Brianna L. Bauer & Nathaniel A. Roethler & Yuli Buckley & Chih-Chia Su & Wei Huang & Rajesh Ramachandran & Maria S. K. Stoll & Edward W. Yu & Derek J. Taylor & Jason A. Mears, 2024. "Structural basis for regulated assembly of the mitochondrial fission GTPase Drp1," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    11. Katherine A. Ray & Joshua D. Lutgens & Ramesh Bista & Jie Zhang & Ronak R. Desai & Melissa Hirsch & Takeshi Miyazawa & Antonio Cordova & Adrian T. Keatinge-Clay, 2024. "Assessing and harnessing updated polyketide synthase modules through combinatorial engineering," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    12. Fan Lu & Liang Zhu & Thomas Bromberger & Jun Yang & Qiannan Yang & Jianmin Liu & Edward F. Plow & Markus Moser & Jun Qin, 2022. "Mechanism of integrin activation by talin and its cooperation with kindlin," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    13. Zengyu Shao & Jiuwei Lu & Nelli Khudaverdyan & Jikui Song, 2024. "Multi-layered heterochromatin interaction as a switch for DIM2-mediated DNA methylation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    14. Yudong Gao & Daichi Shonai & Matthew Trn & Jieqing Zhao & Erik J. Soderblom & S. Alexandra Garcia-Moreno & Charles A. Gersbach & William C. Wetsel & Geraldine Dawson & Dmitry Velmeshev & Yong-hui Jian, 2024. "Proximity analysis of native proteomes reveals phenotypic modifiers in a mouse model of autism and related neurodevelopmental conditions," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    15. Martin F. Peter & Christian Gebhardt & Rebecca Mächtel & Gabriel G. Moya Muñoz & Janin Glaenzer & Alessandra Narducci & Gavin H. Thomas & Thorben Cordes & Gregor Hagelueken, 2022. "Cross-validation of distance measurements in proteins by PELDOR/DEER and single-molecule FRET," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    16. Jutta Diessl & Jens Berndtsson & Filomena Broeskamp & Lukas Habernig & Verena Kohler & Carmela Vazquez-Calvo & Arpita Nandy & Carlotta Peselj & Sofia Drobysheva & Ludovic Pelosi & F.-Nora Vögtle & Fab, 2022. "Manganese-driven CoQ deficiency," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    17. Alexander Kroll & Sahasra Ranjan & Martin K. M. Engqvist & Martin J. Lercher, 2023. "A general model to predict small molecule substrates of enzymes based on machine and deep learning," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    18. Lisa-Marie Appel & Vedran Franke & Johannes Benedum & Irina Grishkovskaya & Xué Strobl & Anton Polyansky & Gregor Ammann & Sebastian Platzer & Andrea Neudolt & Anna Wunder & Lena Walch & Stefanie Kais, 2023. "The SPOC domain is a phosphoserine binding module that bridges transcription machinery with co- and post-transcriptional regulators," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    19. Maciej K. Kocylowski & Hande Aypek & Wolfgang Bildl & Martin Helmstädter & Philipp Trachte & Bernhard Dumoulin & Sina Wittösch & Lukas Kühne & Ute Aukschun & Carolin Teetzen & Oliver Kretz & Botond Ga, 2022. "A slit-diaphragm-associated protein network for dynamic control of renal filtration," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Marie C. Schoelmerich & Lynn Ly & Jacob West-Roberts & Ling-Dong Shi & Cong Shen & Nikhil S. Malvankar & Najwa Taib & Simonetta Gribaldo & Ben J. Woodcroft & Christopher W. Schadt & Basem Al-Shayeb & , 2024. "Borg extrachromosomal elements of methane-oxidizing archaea have conserved and expressed genetic repertoires," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48291-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.