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Domain architecture of BAF250a reveals the ARID and ARM-repeat domains with implication in function and assembly of the BAF remodeling complex

Sandhya, Sankaran and Maulik, Aditi and Giri, Malyasree and Singh, Mahavir (2018) Domain architecture of BAF250a reveals the ARID and ARM-repeat domains with implication in function and assembly of the BAF remodeling complex. In: PLOS ONE, 13 (10).

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Official URL: http://dx.doi.org/10.1371/journal.pone.0205267


BAF250a and BAF250b are subunits of the SWI/SNF chromatin-remodeling complex that recruit the complex to chromatin allowing transcriptional activation of several genes. Despite being the central subunits of the SWI/SNF complex, the structural and functional annotation of BAF250a/b remains poorly understood. BAF250a (nearly 2200 residues protein) harbors an N-terminal DNA binding ARID (similar to 110 residues) and a C-terminal folded region (similar to 250 residues) of unknown structure and function, recently annotated as BAF250_C. Using hydrophobic core analysis, fold prediction and comparative modeling, here we have defined a domain boundary and associate a beta-catenin like ARM-repeat fold to the C-terminus of BAF250a that encompass BAF250_C. The N-terminal DNA-binding ARID is found in diverse domain combinations in proteins imparting unique functions. We used a comparative sequence analysis based approach to study the ARIDs from diverse domain contexts and identified conserved residue positions that are important to preserve its core structure. Supporting this, mutation of one such conserved residue valine, at position 1067, to glycine, resulted in destabilization, loss of structural integrity and DNA binding affinity of ARID. Additionally, we identified a set of conserved and surface-exposed residues unique to the ARID when it co-occurs with the ARM repeat containing BAF250_C in BAF250a. Several of these residues are found mutated in somatic cancers. We predict that these residues in BAF250a may play important roles in mediating protein-DNA and protein-protein interactions in the BAF complex.

Item Type: Journal Article
Additional Information: Copy right for this article belong to PUBLIC LIBRARY SCIENCE
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility)
Depositing User: Id for Latest eprints
Date Deposited: 14 Nov 2018 15:11
Last Modified: 14 Nov 2018 15:11
URI: http://eprints.iisc.ac.in/id/eprint/61054

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