National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM135343
米国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2023 タイトル: Cryo-EM structures of Myomaker reveal a molecular basis for myoblast fusion. 著者: Tao Long / Yichi Zhang / Linda Donnelly / Hui Li / Yu-Chung Pien / Ning Liu / Eric N Olson / Xiaochun Li / 要旨: The fusion of mononucleated myoblasts produces multinucleated muscle fibers leading to the formation of skeletal muscle. Myomaker, a skeletal muscle-specific membrane protein, is essential for ...The fusion of mononucleated myoblasts produces multinucleated muscle fibers leading to the formation of skeletal muscle. Myomaker, a skeletal muscle-specific membrane protein, is essential for myoblast fusion. Here we report the cryo-EM structures of mouse Myomaker (mMymk) and Ciona robusta Myomaker (cMymk). Myomaker contains seven transmembrane helices (TMs) that adopt a G-protein-coupled receptor-like fold. TMs 2-4 form a dimeric interface, while TMs 3 and 5-7 create a lipid-binding site that holds the polar head of a phospholipid and allows the alkyl tails to insert into Myomaker. The similarity of cMymk and mMymk suggests a conserved Myomaker-mediated cell fusion mechanism across evolutionarily distant species. Functional analyses demonstrate the essentiality of the dimeric interface and the lipid-binding site for fusogenic activity, and heterologous cell-cell fusion assays show the importance of transcellular interactions of Myomaker protomers for myoblast fusion. Together, our findings provide structural and functional insights into the process of myoblast fusion.
電子線照射量: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k)
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解析
EMソフトウェア
名称: REFMAC / バージョン: 5.8.0267 / カテゴリ: モデル精密化
CTF補正
タイプ: NONE
3次元再構成
解像度: 3.22 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 145594 / 対称性のタイプ: POINT
精密化
解像度: 3.22→249 Å / Cor.coef. Fo:Fc: 0.754 / Cor.coef. Fo:Fc free: 0.754 / SU B: 11.407 / SU ML: 0.163 / 交差検証法: THROUGHOUT / ESU R: 0.111 / ESU R Free: 0.11 / 立体化学のターゲット値: MAXIMUM LIKELIHOOD / 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
Rfactor
反射数
%反射
Selection details
Rfree
0.45086
50773
5.2 %
RANDOM
Rwork
0.4488
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-
-
obs
0.44891
917698
100 %
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溶媒の処理
イオンプローブ半径: 0.8 Å / 減衰半径: 0.8 Å / VDWプローブ半径: 1.2 Å / 溶媒モデル: MASK