Human SNF5 and BAF155 constitute the core subunit of multi-protein SWI/SNF chromatin-remodeling complexes that are required for ATP-dependent nucleosome mobility and transcriptional control. Human SNF5 (hSNF5) utilizes its repeat 1 (RPT1) domain to associate with the SWIRM domain of BAF155. Here, we employed X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and various biophysical methods in order to investigate the detailed binding mechanism between hSNF5 and BAF155. Multi-angle light scattering data clearly indicate that hSNF5171–258 and BAF155SWIRM are both monomeric in solution and they form a heterodimer. NMR data and crystal structure of the hSNF5171–258 /BAF155SWIRM complex further reveal a unique binding interface, which involves a coil-to-helix transition upon protein binding. The newly formed αN helix of hSNF5171–258 interacts with the β2–α1 loop of hSNF5 via hydrogen bonds and it also displays a hydrophobic interaction with BAF155SWIRM. Therefore, the N-terminal region of hSNF5171–258 plays an important role in tumorigenesis and our data will provide a structural clue for the pathogenesis of Rhabdoid tumors and malignant melanomas that originate from mutations in the N-terminal loop region of hSNF5.
|Journal||International journal of molecular sciences|
|Publication status||Published - 2020 Apr 1|
Bibliographical noteFunding Information:
Funding: This work was supported by several grants (NRF-2017R1A2B2008483, 2019M3A9F6021810, NRF-2017M3A9F6029753, NRF-2019M3E5D6063903 to W. Lee, NRF-20161A6A3A04010213 to J.-H. Yun, NRF-2018R1D1A1B07049312 to K.J. and NRF-2017R1E1A1A01077717 to J.L.), through the National Research Foundation of Korea (NRF) and Brain Korea Plus (BK+) program (J. Han). This research was also supported by the Cooperative Research Program for Agriculture Science & Technology Development, Rural Development Administration, Republic of Korea (PJ011112, PJ01495901), and the Creative-Pioneering Researchers Program, through Seoul National University (SNU).
Acknowledgments: We thank the Research Institute of Agriculture and Life Sciences, the high-field NMR facility at the Korea Institute of Science and Technology, the Korea Basic Science Institute, and the National Center for Inter-University Research Facilities. We would like to express our gratitude to the staff scientists at the NCI station of the Pohang Accelerator Laboratory X-ray Free-Electron Laser, 5C and 7C beamline of the Pohang Accelerator Laboratory.
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry