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Structure and chromosomal DNA binding of the SWIRM domain

Nature Structural & Molecular Biology volume 12, pages 10781085 (2005) | Download Citation

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Abstract

The evolutionarily conserved Swi3p, Rsc8p and Moira (SWIRM) domain is found in many chromosomal proteins involved in chromatin modifications or remodeling. Here we report the three-dimensional solution structure of the SWIRM domain from the human transcriptional adaptor ADA2α. The structure reveals a five-helix bundle consisting of two helix-turn-helix motifs connected by a central long helix, reminiscent of the histone fold. Using structural and biochemical analyses, we showed that the SWIRM domains of human ADA2α and SMARC2 bind to double-stranded and nucleosomal DNA, and we identified amino acid residues required for this function. We demonstrated that the ADA2α SWIRM domain is colocalized with lysine-acetylated histone H3 in the cell nucleus and that it potentiates the ACF remodeling activity by enhancing accessibility of nucleosomal linker DNA bound to histone H1. These data suggest a functional role of the SWIRM domain in chromatin remodeling.

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Acknowledgements

The authors gratefully acknowledge M. Bauck for critical reading of the manuscript, S. Mujtaba for technical help and S. Hearn at Cold Spring Harbor Laboratory Microscopy Facility for technical assistance in performing the confocal laser scanning microscopy. This work was supported by grants from the US National Institutes of Health to M.-M.Z. and M.J.W.

Author information

Author notes

    • Chengmin Qian
    •  & Qiang Zhang

    These authors contributed equally to this work.

Affiliations

  1. Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, One Gustave L. Levy Place, New York, New York 10029, USA.

    • Chengmin Qian
    • , Qiang Zhang
    • , Lei Zeng
    •  & Ming-Ming Zhou
  2. Department of Pediatrics, Mount Sinai School of Medicine, New York University, One Gustave L. Levy Place, New York, New York 10029, USA.

    • SiDe Li
    •  & Martin J Walsh

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The authors declare no competing financial interests.

Corresponding authors

Correspondence to Martin J Walsh or Ming-Ming Zhou.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Structure-based sequence alignment of SWIRM domains.

  2. 2.

    Supplementary Fig. 2

    Three-dimensional NMR structure of the human ADA2α SWIRM domain.

  3. 3.

    Supplementary Fig. 3

    Assessment of the R428A mutation effect on the ADA2 SWIRM domain structure.

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DOI

https://doi.org/10.1038/nsmb1022