7cyu
Crystal structure of human BAF57 HMG domain
Structural highlights
DiseaseSMCE1_HUMAN Familial multiple meningioma;Coffin-Siris syndrome. 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. FunctionSMCE1_HUMAN Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. 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). Required for the coactivation of estrogen responsive promoters by SWI/SNF complexes and the SRC/p160 family of histone acetyltransferases (HATs). Also specifically interacts with the CoREST corepressor resulting in repression of neuronal specific gene promoters in non-neuronal cells.[UniProtKB:O54941][1] [2] [3] Publication Abstract from PubMedThe SWI/SNF chromatin remodeling complex plays important roles in gene regulation and it is classified as the SWI/SNF complex in yeast and BAF complex in vertebrates. BAF57, one of the subunits that forms the chromatin remodeling complex core, is well conserved in the BAF complex of vertebrates, which is replaced by bap111 in the Drosophila BAP complex and does not have a counterpart in the yeast SWI/SNF complex. This suggests that BAF57 is a key component of the chromatin remodeling complex in higher eukaryotes. BAF57 contains a HMG domain, which is widely distributed among various proteins and functions as a DNA binding motif. Most proteins with HMG domain bind to four-way junction (4WJ) DNA. Here, we report the crystal structure of the HMG domain of BAF57 (BAF57(HMG)) at a resolution of 2.55 A. The structure consists of three alpha-helices and adopts an L-shaped form. The overall structure is stabilized by a hydrophobic core, which is formed by hydrophobic residues. The binding affinity between BAF57(HMG) and 4WJ DNA is determined as a 295.83 +/- 1.05 nM using a fluorescence quenching assay, and the structure revealed 4WJ DNA binding site of BAF57(HMG). Our data will serve structural basis in understanding the roles of BAF57 during chromatin remodeling process. Crystal structure of the HMG domain of human BAF57 and its interaction with four-way junction DNA.,Heo Y, Park JH, Kim J, Han J, Yun JH, Lee W Biochem Biophys Res Commun. 2020 Sep 30. pii: S0006-291X(20)31847-7. doi:, 10.1016/j.bbrc.2020.09.094. PMID:33010889[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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