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The SAM domain of mouse SAMHD1 is critical for its activation and regulation

Author

Listed:
  • Olga Buzovetsky

    (Yale University)

  • Chenxiang Tang

    (Yale University)

  • Kirsten M. Knecht

    (Yale University)

  • Jenna M. Antonucci

    (The Ohio State University)

  • Li Wu

    (The Ohio State University)

  • Xiaoyun Ji

    (Nanjing University)

  • Yong Xiong

    (Yale University)

Abstract

Human SAMHD1 (hSAMHD1) is a retroviral restriction factor that blocks HIV-1 infection by depleting the cellular nucleotides required for viral reverse transcription. SAMHD1 is allosterically activated by nucleotides that induce assembly of the active tetramer. Although the catalytic core of hSAMHD1 has been studied extensively, previous structures have not captured the regulatory SAM domain. Here we report the crystal structure of full-length SAMHD1 by capturing mouse SAMHD1 (mSAMHD1) structures in three different nucleotide bound states. Although mSAMHD1 and hSAMHD1 are highly similar in sequence and function, we find that mSAMHD1 possesses a more complex nucleotide-induced activation process, highlighting the regulatory role of the SAM domain. Our results provide insights into the regulation of SAMHD1 activity, thereby facilitating the improvement of HIV mouse models and the development of new therapies for certain cancers and autoimmune diseases.

Suggested Citation

  • Olga Buzovetsky & Chenxiang Tang & Kirsten M. Knecht & Jenna M. Antonucci & Li Wu & Xiaoyun Ji & Yong Xiong, 2018. "The SAM domain of mouse SAMHD1 is critical for its activation and regulation," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02783-8
    DOI: 10.1038/s41467-017-02783-8
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    Cited by:

    1. Priya Kapoor-Vazirani & Sandip K. Rath & Xu Liu & Zhen Shu & Nicole E. Bowen & Yitong Chen & Ramona Haji-Seyed-Javadi & Waaqo Daddacha & Elizabeth V. Minten & Diana Danelia & Daniela Farchi & Duc M. D, 2022. "SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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