7lhy | pdb_00007lhy

Caenorhabditis elegans SWSN-4 (SMARCA4-BRG1) ATPase Bromodomain in complex with a modified histone H3, N6-epsilon-acetyl-L-lysine 14 (H3K14ac) polypeptide

spinqualitylabelsall models 7lhy, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7lhy is a 2 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.3Å Ligands: ALY Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G5EF53_CAEEL Publication Abstract from PubMed Bromodomains (BD) are conserved reader modules that bind acetylated lysine residues on histones. Although much has been learned regarding the in vitro properties of these domains, less is known about their function within chromatin complexes. SWI/SNF chromatin-remodeling complexes modulate transcription and contribute to DNA damage repair. Mutations in SWI/SNF subunits have been implicated in many cancers. Here we demonstrate that the BD of Caenorhabditis elegans SMARCA4/BRG1, a core SWI/SNF subunit, recognizes acetylated lysine 14 of histone H3 (H3K14ac), similar to its Homo sapiens ortholog. We identify the interactions of SMARCA4 with the acetylated histone peptide from a 1.29 A-resolution crystal structure of the CeSMARCA4 BD-H3K14ac complex. Significantly, most of the SMARCA4 BD residues in contact with the histone peptide are conserved with other proteins containing family VIII bromodomains. Based on the premise that binding specificity is conserved among bromodomain orthologs, we propose that loop residues outside of the binding pocket position contact residues to recognize the H3K14ac sequence. CRISPR-Cas9-mediated mutations in the SMARCA4 BD that abolish H3K14ac binding in vitro had little or no effect on C. elegans viability or physiological function in vivo. However, combining SMARCA4 BD mutations with knockdown of the SWI/SNF accessory subunit PBRM-1 resulted in severe developmental defects in animals. In conclusion, we demonstrated an essential function for the SWI/SNF bromodomain in vivo and detected potential redundancy in epigenetic readers in regulating chromatin remodeling. These findings have implications for the development of small-molecule BD inhibitors to treat cancers and other diseases. Binding specificity and function of the SWI/SNF subunit SMARCA4 bromodomain interaction with acetylated histone H3K14.,Enriquez P, Krajewski K, Strahl BD, Rothbart SB, Dowen RH, Rose RB J Biol Chem. 2021 Oct;297(4):101145. doi: 10.1016/j.jbc.2021.101145. Epub 2021 , Aug 30. PMID:34473995 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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