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Crystal structure of the FTO protein reveals basis for its substrate specificity

Author

Listed:
  • Zhifu Han

    (National Institute of Biological Sciences, No. 7 Science Park Road, Beijing 102206, China)

  • Tianhui Niu

    (National Institute of Biological Sciences, No. 7 Science Park Road, Beijing 102206, China
    College of Biological Sciences, China Agricultural University)

  • Junbiao Chang

    (Zhengzhou University)

  • Xiaoguang Lei

    (National Institute of Biological Sciences, No. 7 Science Park Road, Beijing 102206, China
    School of Pharmaceutical Science and Technology, Tianjin University)

  • Mingyan Zhao

    (National Institute of Biological Sciences, No. 7 Science Park Road, Beijing 102206, China)

  • Qiang Wang

    (Zhengzhou University)

  • Wei Cheng

    (National Institute of Biological Sciences, No. 7 Science Park Road, Beijing 102206, China)

  • Jinjing Wang

    (National Institute of Biological Sciences, No. 7 Science Park Road, Beijing 102206, China)

  • Yi Feng

    (National Institute of Biological Sciences, No. 7 Science Park Road, Beijing 102206, China)

  • Jijie Chai

    (National Institute of Biological Sciences, No. 7 Science Park Road, Beijing 102206, China
    Tsinghua University)

Abstract

How FTO targets obesity The fat mass and obesity-associated (FTO) gene is associated with increased body weight and obesity risk. FTO protein is a DNA/RNA demethylase, and mice lacking it are abnormally lean. Now the crystal structure of human FTO in complex with the mononucleotide 3-meT has been determined. The structure reveals a novel mechanism by which the protein can discriminate between single- and double-stranded DNA. In addition, biochemical assays show that the C-terminal domain of FTO, previously of unknown function, is required for FTO catalytic activity via interactions with the N-terminal catalytic domain. These results provide a structural basis for understanding FTO substrate specificity, and serve as a foundation for the rational design of FTO inhibitors as potential anti-obesity agents.

Suggested Citation

  • Zhifu Han & Tianhui Niu & Junbiao Chang & Xiaoguang Lei & Mingyan Zhao & Qiang Wang & Wei Cheng & Jinjing Wang & Yi Feng & Jijie Chai, 2010. "Crystal structure of the FTO protein reveals basis for its substrate specificity," Nature, Nature, vol. 464(7292), pages 1205-1209, April.
    • Handle: RePEc:nat:nature:v:464:y:2010:i:7292:d:10.1038_nature08921
    DOI: 10.1038/nature08921
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    Cited by:

    1. Yuwei Zhang & Jieyu Zhao & Xiaona Chen & Yulong Qiao & Jinjin Kang & Xiaofan Guo & Feng Yang & Kaixin Lyu & Yiliang Ding & Yu Zhao & Hao Sun & Chun-Kit Kwok & Huating Wang, 2024. "DHX36 binding induces RNA structurome remodeling and regulates RNA abundance via m6A reader YTHDF1," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Yolanda Saldaña-Alvarez & María Guadalupe Salas-Martínez & Humberto García-Ortiz & Angélica Luckie-Duque & Gustavo García-Cárdenas & Hermenegildo Vicenteño-Ayala & Emilio J Cordova & Marcelino Esparza, 2016. "Gender-Dependent Association of FTO Polymorphisms with Body Mass Index in Mexicans," PLOS ONE, Public Library of Science, vol. 11(1), pages 1-12, January.

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