Crystal structure of the N-terminal methyltransferase-like domain of anamorsin

Authors

  • Gaojie Song,

    1. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
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    • Gaojie Song and Chongyun Cheng contributed equally to this work

  • Chongyun Cheng,

    1. iHuman Institute, ShanghaiTech University, Shanghai, China
    2. Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
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    • Gaojie Song and Chongyun Cheng contributed equally to this work

  • Yang Li,

    1. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
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  • Neil Shaw,

    1. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
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  • Zhi-Cheng Xiao,

    Corresponding author
    1. Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
    • Correspondence to: Zhi-Cheng Xiao, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia. E-mail: zhicheng.xiao@monash.edu or

      Zhi-Jie Liu, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. E-mail: zjliu@ibp.ac.cn

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  • Zhi-Jie Liu

    Corresponding author
    1. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    2. iHuman Institute, ShanghaiTech University, Shanghai, China
    • Correspondence to: Zhi-Cheng Xiao, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia. E-mail: zhicheng.xiao@monash.edu or

      Zhi-Jie Liu, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. E-mail: zjliu@ibp.ac.cn

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ABSTRACT

Anamorsin is a recently identified molecule that inhibits apoptosis during hematopoiesis. It contains an N-terminal methyltransferase-like domain and a C-terminal Fe-S cluster motif. Not much is known about the function of the protein. To better understand the function of anamorsin, we have solved the crystal structure of the N-terminal domain at 1.8 Å resolution. Although the overall structure resembles a typical S-adenosylmethionine (SAM) dependent methyltransferase fold, it lacks one α-helix and one β-strand. As a result, the N-terminal domain as well as the full-length anamorsin did not show S-adenosyl-l-methionine (AdoMet) dependent methyltransferase activity. Structural comparisons with known AdoMet dependent methyltransferases reveals subtle differences in the SAM binding pocket that preclude the N-terminal domain from binding to AdoMet. The N-terminal methyltransferase-like domain of anamorsin probably functions as a structural scaffold to inhibit methyl transfers by out-competing other AdoMet dependant methyltransferases or acts as bait for protein–protein interactions.Proteins 2014; 82:1066–1071. © 2013 Wiley Periodicals, Inc.

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