6YXO

Structure of the N-terminal module of the human SWI/SNF-subunit BAF155/SMARCC1

Summary for 6YXO

• Entry DOI: 10.2210/pdb6yxo/pdb
• Descriptor: SWI/SNF complex subunit SMARCC1 (2 entities in total)
• Functional Keywords: baf155, swi/snf-subunit, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 65412.23

Authors

Allen, M.D.,Bycroft, M.,Zinzalla, G. (deposition date: 2020-05-03, release date: 2021-04-21, Last modification date: 2021-11-03)

Primary citation

Allen, M.D.,Freund, S.M.V.,Bycroft, M.,Zinzalla, G.
SWI/SNF subunit BAF155 N-terminus structure informs the impact of cancer-associated mutations and reveals a potential drug binding site.
Commun Biol, 4:528-528, 2021

PubMed Abstract: SWI/SNF (BAF) chromatin remodelling complexes are key regulators of gene expression programs, and attractive drug targets for cancer therapies. Here we show that the N-terminus of the BAF155/SMARCC1 subunit contains a putative DNA-binding MarR-like domain, a chromodomain and a BRCT domain that are interconnected to each other to form a distinct module. In this structure the chromodomain makes interdomain interactions and has lost its canonical function to bind to methylated lysines. The structure provides new insights into the missense mutations that target this module in cancer. This study also reveals two adjacent, highly-conserved pockets in a cleft between the domains that form a potential binding site, which can be targeted with small molecules, offering a new strategy to target SWI/SNF complexes.

PubMed: 33953332
DOI: 10.1038/s42003-021-02050-z

Experimental method

X-RAY DIFFRACTION (2 Å)