6lzp
From Proteopedia
The solution structure of N-terminal elongated hSNF5 RPT1 domain
Structural highlights
Disease[SNF5_HUMAN] Neurofibromatosis type 3;Atypical teratoid rhabdoid tumor;Familial rhabdoid tumor;Familial multiple meningioma;Coffin-Siris syndrome. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function[SNF5_HUMAN] Core component of the BAF (hSWI/SNF) complex. This ATP-dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation. The BAF complex is able to create a stable, altered form of chromatin that constrains fewer negative supercoils than normal. This change in supercoiling would be due to the conversion of up to one-half of the nucleosomes on polynucleosomal arrays into asymmetric structures, termed altosomes, each composed of 2 histones octamers. Stimulates in vitro the remodeling activity of SMARCA4/BRG1/BAF190A. Involved in activation of CSF1 promoter. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Plays a key role in cell-cycle control and causes cell cycle arrest in G0/G1.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedHuman 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 alphaN helix of hSNF5(171-258) interacts with the beta2-alpha1 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. A Coil-to-Helix Transition Serves as a Binding Motif for hSNF5 and BAF155 Interaction.,Han J, Kim I, Park JH, Yun JH, Joo K, Kim T, Park GY, Ryu KS, Ko YJ, Mizutani K, Park SY, Seong RH, Lee J, Suh JY, Lee W Int J Mol Sci. 2020 Apr 1;21(7). pii: ijms21072452. doi: 10.3390/ijms21072452. PMID:32244797[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||
Categories: Homo sapiens | Large Structures | Han J | Kim I | Lee W | Suh JY
