ジャーナル: Structure / 年: 2021 タイトル: Structural study of the N-terminal domain of human MCM8/9 complex. 著者: Jun Li / Daqi Yu / Lan Liu / Huanhuan Liang / Qi Ouyang / Yingfang Liu / 要旨: MCM8/9 is a complex involved in homologous recombination (HR) repair pathway. MCM8/9 dysfunction can cause genome instability and result in primary ovarian insufficiency (POI). However, the mechanism ...MCM8/9 is a complex involved in homologous recombination (HR) repair pathway. MCM8/9 dysfunction can cause genome instability and result in primary ovarian insufficiency (POI). However, the mechanism underlying these effects is largely unknown. Here, we report crystal structures of the N-terminal domains (NTDs) of MCM8 and MCM9, and build a ring-shaped NTD structure based on a 6.6 Å resolution cryoelectron microscopy map. This shows that the MCM8/9 complex forms a 3:3 heterohexamer in an alternating pattern. A positively charged DNA binding channel and a putative ssDNA exit pathway for fork DNA unwinding are revealed. Based on the atomic model, the potential effects of the clinical POI mutants are interpreted. Surprisingly, the zinc-finger motifs are found to be capable of binding an iron atom as well. Overall, our results provide a model for the formation of the MCM8/9 complex and provide a path for further studies.
ソフトウェア - 名称: Gctf (ver. 1.06) 詳細: The CTF correction was performed in Relion automatically, using the defocus values calculated by Gctf software.
初期モデル
モデルのタイプ: INSILICO MODEL / 詳細: Generated by CryoSPARC software
最終 再構成
想定した対称性 - 点群: C1 (非対称) / アルゴリズム: BACK PROJECTION / 解像度のタイプ: BY AUTHOR / 解像度: 6.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION (ver. 2.1) 詳細: The structure is obtained by focused refinement for N terminal domain of MCM 8/9 full complex 使用した粒子像数: 184677
初期 角度割当
タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: RELION (ver. 2.1)
最終 角度割当
タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: RELION (ver. 2.1)