Neuropathic MORC2 mutations perturb GHKL ATPase dimerization dynamics and epigenetic silencing by multiple structural mechanisms

Christopher H. Douse; Stuart Bloor; Yangci Liu; Maria Shamin; Iva A. Tchasovnikarova; Richard T. Timms; Paul J. Lehner; Yorgo Modis

doi:10.1038/s41467-018-03045-x

Nature Communications (Feb 2018)

Neuropathic MORC2 mutations perturb GHKL ATPase dimerization dynamics and epigenetic silencing by multiple structural mechanisms

Christopher H. Douse,
Stuart Bloor,
Yangci Liu,
Maria Shamin,
Iva A. Tchasovnikarova,
Richard T. Timms,
Paul J. Lehner,
Yorgo Modis

Affiliations

Christopher H. Douse: Department of Medicine, MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, University of Cambridge
Stuart Bloor: Department of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, University of Cambridge
Yangci Liu: Department of Medicine, MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, University of Cambridge
Maria Shamin: Department of Medicine, MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, University of Cambridge
Iva A. Tchasovnikarova: Department of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, University of Cambridge
Richard T. Timms: Department of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, University of Cambridge
Paul J. Lehner: Department of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, University of Cambridge
Yorgo Modis: Department of Medicine, MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, University of Cambridge

DOI: https://doi.org/10.1038/s41467-018-03045-x
Journal volume & issue: Vol. 9, no. 1
pp. 1 – 15

Abstract

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Microrchidia CW-type zinc finger protein 2 (MORC2) is an effector of epigenetic silencing by the human silencing hub (HUSH). Here the authors present the crystal structures of MORC2 and disease-causing MORC2 mutants and give mechanistic insights into how MORC2 mediates HUSH-dependent silencing.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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