Structure Basis for Shaping the Nse4 Protein by the Nse1 and Nse3 Dimer within the Smc5/6 Complex

JOURNAL OF MOLECULAR BIOLOGY

卷:433

Article

Jo, Aera¹  Li, Shibai²  Shin, Jin Woo¹  Zhao, Xiaolan²  Cho, Yunje¹ 

[1] Pohang Univ Sci & Technol, Dept Life Sci, Pohang, South Korea

[2] Mem Sloan Kettering Canc Ctr, Mol Biol Program, New York, NY 10065 USA

关键词: the Smc5/6 complex;    Nse1-Nse3-Nse4;    kleisin-KITE complex;    DNA replication and repair;    chromosome structure;   

DOI  :  10.1016/j.jmb.2021.166910

来源: Elsevier

【 摘 要 】

The Smc5/6 complex facilitates chromosome replication and DNA break repair. Within this complex, a subcomplex composed of Nse1, Nse3 and Nse4 is thought to play multiple roles through DNA binding and regulating ATP-dependent activities of the complex. However, how the Nse1-Nse3-Nse4 subcomplex carries out these multiple functions remain unclear. To address this question, we determine the crystal structure of the Xenopus laevis Nse1-Nse3-Nse4 subcomplex at 1.7 angstrom resolution and examine how it interacts with DNA. Our structural analyses show that the Nse1-Nse3 dimer adopts a closed conformation and forms three interfaces with a segment of Nse4, forcing it into a Z-shaped conformation. The Nse1-Nse3-Nse4 structure provides an explanation for how the lung disease immunodeficiency and chromosome breakage syndrome-causing mutations could dislodge Nse4 from Nse1-Nse3. Our DNA binding and mutational analyses reveal that the N-terminal and the middle region of Nse4 contribute to DNA interaction and cell viability. Integrating our data with previous crosslink mass spectrometry data, we propose potential roles of the Nse1-Nse3-Nse4 complex in binding DNA within the Smc5/6 complex. (C) 2021 Elsevier Ltd. All rights reserved.

【 授权许可】

Free