A coil-to-helix transition serves as a binding motif for hSNF5 and BAF155 interaction

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 hSNF5^171–258 and BAF155^SWIRM are both monomeric in solution and they form a heterodimer. NMR data and crystal structure of the hSNF5^171–258 /BAF155^SWIRM complex further reveal a unique binding interface, which involves a coil-to-helix transition upon protein binding. The newly formed α_N helix of hSNF5^171–258 interacts with the β2–α1 loop of hSNF5 via hydrogen bonds and it also displays a hydrophobic interaction with BAF155^SWIRM. Therefore, the N-terminal region of hSNF5^171–258 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.