|
|||||
|
|
Structure Basis for Shaping the Nse4 Protein by the Nse1 and Nse3 Dimer within the Smc5/6 Complex |
|
| Institution: | 1. Department of Life Science, Pohang University of Science and Technology, Pohang, Republic of Korea;2. Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;1. Cell Biology and Biophysics Unit, Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany;1. Chromosome Dynamics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan;2. Department of Life Science, College of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo, 171-8501, Japan;3. Department of Biology, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka 558-8585, Japan;1. Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;2. Programs in Biochemistry, Cell, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA;3. Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA;4. Donnelly Centre and Department of Biochemistry, University of Toronto, Toronto, ON M5S 3E1, Canada;5. IFOM, The FIRC of Molecular Oncology, Via Adamello 16, 20139, Milan, Italy;6. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;7. Institute of Biochemistry, Swiss Federal Institute of Technology in Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland;1. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;2. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;3. Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;4. J. Craig Venter Institute, 9714 Medical Center Drive, Rockville, MD 20850, USA;1. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan;2. Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan |
| Abstract: | 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 Å 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. |
| Keywords: | the Smc5/6 complex Nse1-Nse3-Nse4 kleisin-KITE complex DNA replication and repair chromosome structure SMC"} {"#name":"keyword" "$":{"id":"k0035"} "$$":[{"#name":"text" "_":"structural maintenance of chromosomes NSE"} {"#name":"keyword" "$":{"id":"k0045"} "$$":[{"#name":"text" "_":"Non-SMC elements HAWK"} {"#name":"keyword" "$":{"id":"k0055"} "$$":[{"#name":"text" "_":"HEAT proteins associated with kleisin KITE"} {"#name":"keyword" "$":{"id":"k0065"} "$$":[{"#name":"text" "_":"kleisin-interacting tandem winged-helix elements WH"} {"#name":"keyword" "$":{"id":"k0075"} "$$":[{"#name":"text" "_":"winged helix HTH"} {"#name":"keyword" "$":{"id":"k0085"} "$$":[{"#name":"text" "_":"helix-turn-helix MAGEs"} {"#name":"keyword" "$":{"id":"k0095"} "$$":[{"#name":"text" "_":"melanoma-associated antigens LICS"} {"#name":"keyword" "$":{"id":"k0105"} "$$":[{"#name":"text" "_":"lung disease immunodeficiency and chromosome breakage syndrome Nse4M"} {"#name":"keyword" "$":{"id":"k0115"} "$$":[{"#name":"text" "_":"Nse4 middle domain CL-MS"} {"#name":"keyword" "$":{"id":"k0125"} "$$":[{"#name":"text" "_":"crosslink and mass spectrometry Y2H"} {"#name":"keyword" "$":{"id":"k0135"} "$$":[{"#name":"text" "_":"yeast two-hybrid analyses |
| 本文献已被 ScienceDirect 等数据库收录！ | |