SMCHD1's ubiquitin-like domain is required for N-terminal dimerization and chromatin localization.

The Biochemical Journal
Alexandra D GurzauJ. M. Murphy

Abstract

Structural maintenance of chromosomes flexible hinge domain-containing 1 (SMCHD1) is an epigenetic regulator that mediates gene expression silencing at targeted sites across the genome. Our current understanding of SMCHD1's molecular mechanism, and how substitutions within SMCHD1 lead to the diseases, facioscapulohumeral muscular dystrophy (FSHD) and Bosma arhinia microphthalmia syndrome (BAMS), are only emerging. Recent structural studies of its two component domains - the N-terminal ATPase and C-terminal SMC hinge - suggest that dimerization of each domain plays a central role in SMCHD1 function. Here, using biophysical techniques, we demonstrate that the SMCHD1 ATPase undergoes dimerization in a process that is dependent on both the N-terminal UBL (Ubiquitin-like) domain and ATP binding. We show that neither the dimerization event, nor the presence of a C-terminal extension past the transducer domain, affect SMCHD1's in vitro catalytic activity as the rate of ATP turnover remains comparable to the monomeric protein. We further examined the functional importance of the N-terminal UBL domain in cells, revealing that its targeted deletion disrupts the localization of full-length SMCHD1 to chromatin. These findings implicate UBL...Continue Reading

References

Jan 19, 2000·Trends in Biochemical Sciences·R Dutta, M Inouye
Nov 22, 2001·The Journal of Biological Chemistry·Mark C HallThomas A Kunkel
May 2, 2002·Molecular Cell·Christian H HaeringKim Nasmyth
Sep 18, 2002·The Journal of Biological Chemistry·Klaus RichterJohannes Buchner
Nov 24, 2004·Analytical Biochemistry·Borries Demeler, Kensal E van Holde
Jun 9, 2005·Structure·Kevin D Corbett, James M Berger
Aug 16, 2005·The Journal of Biological Chemistry·Hua WeiGregory L Verdine
Apr 21, 2006·Nature·Maruf M U AliLaurence H Pearl
Jul 4, 2008·Nature·Christian H HaeringKim Nasmyth
Jun 2, 2012·Protein Science : a Publication of the Protein Society·Christian N CunninghamDavid A Agard
Jan 9, 2013·Methods in Molecular Biology·Jeffrey J Babon, James M Murphy
Jan 29, 2013·Nature Structural & Molecular Biology·Frank BürmannStephan Gruber
Jun 12, 2013·Molecular and Cellular Biology·Anne-Valerie GendrelNeil Brockdorff
Apr 1, 2012·Journal of Applied Crystallography·Maxim V PetoukhovDmitri I Svergun
Jun 21, 2015·Proceedings of the National Academy of Sciences of the United States of America·Kelan ChenMarnie E Blewitt
Apr 10, 2016·The Biochemical Journal·Kelan ChenJames M Murphy
Apr 25, 2016·Methods in Molecular Biology·Andrew J Kueh, Marco J Herold
Aug 17, 2016·Proceedings of the National Academy of Sciences of the United States of America·Sisi LiSteven E Jacobsen
Dec 6, 2016·Acta Crystallographica. Section D, Structural Biology·Nigel KirbyTimothy M Ryan
Feb 23, 2017·Trends in Genetics : TIG·Natasha JanszMarnie E Blewitt
May 12, 2018·The Journal of Biological Chemistry·Alexandra D GurzauJames M Murphy
Aug 22, 2018·Nature Structural & Molecular Biology·Natasha JanszMarnie E Blewitt
Oct 30, 2018·Protein Science : a Publication of the Protein Society·Vassili PiiadovIgor Polikarpov
Nov 30, 2018·Proceedings of the National Academy of Sciences of the United States of America·Hyoung Tae Kim, Alfred L Goldberg
Jan 12, 2020·Communications Biology·Lars C PedersenNatalie D Shaw
Feb 20, 2020·Proceedings of the National Academy of Sciences of the United States of America·Galen A Collins, Alfred L Goldberg
Aug 12, 2020·Biochemical Society Transactions·Alexandra D GurzauRichard W Birkinshaw
Nov 14, 2020·ELife·Iromi WanigasuriyaMarnie E Blewitt

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