6MW7

Crystal structure of ATPase module of SMCHD1 bound to ATP

6MW7 の概要

• エントリーDOI: 10.2210/pdb6mw7/pdb
• 分子名称: Structural maintenance of chromosomes flexible hinge domain-containing protein 1, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: ghkl-atpase, epigenetic repressor, bosma arhinia microphthalmia, fascioscapulohumeral muscular dystrophy type 2, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 263231.01

構造登録者

Pedersen, L.C.,Inoue, K.,Kim, S.,Perera, L.,Shaw, N.D. (登録日: 2018-10-29, 公開日: 2019-09-11, 最終更新日: 2024-10-09)

主引用文献

Pedersen, L.C.,Inoue, K.,Kim, S.,Perera, L.,Shaw, N.D.
A ubiquitin-like domain is required for stabilizing the N-terminal ATPase module of human SMCHD1.
Commun Biol, 2:255-255, 2019

PubMed Abstract: Variants in the gene , which encodes an epigenetic repressor, have been linked to both congenital arhinia and a late-onset form of muscular dystrophy called facioscapulohumeral muscular dystrophy type 2 (FSHD2). This suggests that SMCHD1 has a diversity of functions in both developmental time and space. The C-terminal end of SMCHD1 contains an SMC-hinge domain which mediates homodimerization and chromatin association, whereas the molecular architecture of the N-terminal region, which harbors the GHKL-ATPase domain, is not well understood. We present the crystal structure of the human SMCHD1 N-terminal ATPase module bound to ATP as a functional dimer. The dimer is stabilized by a novel N-terminal ubiquitin-like fold and by a downstream transducer domain. While disease variants map to what appear to be critical interdomain/intermolecular interfaces, only the FSHD2-specific mutant constructs we tested consistently abolish ATPase activity and/or dimerization. These data suggest that the full functional profile of SMCHD1 has yet to be determined.

PubMed: 31312724
DOI: 10.1038/s42003-019-0499-y

実験手法

X-RAY DIFFRACTION (2.194 Å)