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The complex structures of ALKBH2 mutants cross-linked to dsDNA reveal the conformational swing of β-hairpin

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Abstract

Mammalian AlkB homologue 2 (ALKBH2) is the primary housekeeping DNA demethylase, effectively repairing endogenously formed methylated lesions in double-stranded DNA. Our previous studies demonstrated that a hydrophobic β-hairpin motif of ALKBH2 could play crucial roles in base-pair stability interrogation and damaged base flipping. Using chemical cross-linking strategy, we obtained two crystal structures of human ALKBH2 mutant bound to duplex DNA. The structural analysis suggests that the β-hairpin motif is flexible in conformation and is likely to slide along the DNA duplex in local regions to search for damaged base. This study provides a new mechanistic insight into DNA damage detection by ALKBH2.

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Authors and Affiliations

  1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    BaoEn Chen & CaiGuang Yang

  2. School of Life Sciences, Fudan University, Shanghai, 200433, China

    JianHua Gan

Authors
  1. BaoEn Chen
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  2. JianHua Gan
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  3. CaiGuang Yang
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Correspondence to JianHua Gan or CaiGuang Yang.

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Chen, B., Gan, J. & Yang, C. The complex structures of ALKBH2 mutants cross-linked to dsDNA reveal the conformational swing of β-hairpin. Sci. China Chem. 57, 307–313 (2014). https://doi.org/10.1007/s11426-013-5029-z

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  • DOI: https://doi.org/10.1007/s11426-013-5029-z

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