6mr4
Crystal structure of the Sth1 bromodomain from S.cerevisiaeCrystal structure of the Sth1 bromodomain from S.cerevisiae
Structural highlights
FunctionSTH1_YEAST Catalytic component of the chromatin structure-remodeling complex (RSC), which is involved in transcription regulation and nucleosome positioning. RSC is responsible for the transfer of a histone octamer from a nucleosome core particle to naked DNA. The reaction requires ATP and involves an activated RSC-nucleosome intermediate. Remodeling reaction also involves DNA translocation, DNA twist and conformational change. As a reconfigurer of centromeric and flanking nucleosomes, RSC complex is required both for proper kinetochore function in chromosome segregation and, via a PKC1-dependent signaling pathway, for organization of the cellular cytoskeleton. This subunit is the essential ATPase of the complex. It is a DNA translocase capable of nucleosome remodeling. Required for full expression of early meiotic genes. Essential for mitotic growth and repression of CHA1 expression. Also involved in G2 phase control.[1] [2] [3] [4] [5] [6] [7] [8] Publication Abstract from PubMedBromodomains recognize a wide range of acetylated lysines in histones and other nuclear proteins. Substrate specificity is critical for their biological function and arises from unique acetyl-lysine binding sites formed by variable loop regions. Here, we analyzed substrate affinity and specificity of the yeast ScSth1p bromodomain, an essential component of the "Remodels the Structure of Chromatin" complex, and found that the wild-type bromodomain preferentially recognizes H3K14ac and H4K20ac peptides. Mutagenesis studies-guided by our crystal structure determined at 2.7-A resolution-revealed loop residues Ser1276 and Trp1338 as key determinants for such interactions. Strikingly, point mutations of each of these residues substantially increased peptide binding affinity and selectivity, respectively. Our data demonstrate that the ScSth1p bromodomain is not optimized for binding to an individual acetylation mark, but fine-tuned for interactions with several such modifications, consistent with the versatile and multivalent nature of histone recognition by reader modules such as bromodomains. Substrate Affinity and Specificity of the ScSth1p Bromodomain Are Fine-Tuned for Versatile Histone Recognition.,Blus BJ, Hashimoto H, Seo HS, Krolak A, Debler EW Structure. 2019 Jul 9. pii: S0969-2126(19)30208-4. doi:, 10.1016/j.str.2019.06.009. PMID:31327661[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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