دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: SMCHD1's ubiquitin-like domain is required for N-terminal dimerization and chromatin localization.
المؤلفون: Gurzau AD; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia., Horne CR; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia., Mok YF; Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria 3010, Australia., Iminitoff M; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia., Willson TA; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia., Young SN; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia., Blewitt ME; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia., Murphy JM; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia.
المصدر: The Biochemical journal [Biochem J] 2021 Jul 16; Vol. 478 (13), pp. 2555-2569.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Published by Portland Press on behalf of the Biochemical Society Country of Publication: England NLM ID: 2984726R Publication Model: Print Cited Medium: Internet ISSN: 1470-8728 (Electronic) Linking ISSN: 02646021 NLM ISO Abbreviation: Biochem J Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London, UK : Published by Portland Press on behalf of the Biochemical Society
مواضيع طبية MeSH: Protein Multimerization*, Chromatin/*metabolism , Chromosomal Proteins, Non-Histone/*chemistry , Chromosomal Proteins, Non-Histone/*metabolism, Adenosine Triphosphatases/genetics ; Adenosine Triphosphatases/metabolism ; Adenosine Triphosphate/metabolism ; Binding Sites/genetics ; Chromatin/genetics ; Chromosomal Proteins, Non-Histone/genetics ; HEK293 Cells ; Humans ; Immunoblotting ; Microscopy, Fluorescence ; Mutation ; Protein Binding ; Protein Domains ; Scattering, Small Angle ; Substrate Specificity ; Ubiquitin/chemistry ; Ubiquitin/metabolism ; X-Ray Diffraction
مستخلص: 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-mediated SMCHD1 dimerization as a crucial step for chromatin interaction, and thereby for promoting SMCHD1-mediated gene silencing.
(© 2021 The Author(s).)
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فهرسة مساهمة: Keywords: GHKL ATPase; SMC proteins; UBL domain; nucleic acid binding proteins; protein–protein interactions
المشرفين على المادة: 0 (Chromatin)
0 (Chromosomal Proteins, Non-Histone)
0 (SMCHD1 protein, human)
0 (Ubiquitin)
8L70Q75FXE (Adenosine Triphosphate)
EC 3.6.1.- (Adenosine Triphosphatases)
تواريخ الأحداث: Date Created: 20210610 Date Completed: 20211129 Latest Revision: 20211129
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8286825
DOI: 10.1042/BCJ20210278
PMID: 34109974
قاعدة البيانات: MEDLINE
الوصف
تدمد:1470-8728
DOI:10.1042/BCJ20210278