6MR4

Crystal structure of the Sth1 bromodomain from S.cerevisiae

Summary for 6MR4

• Entry DOI: 10.2210/pdb6mr4/pdb
• Descriptor: Nuclear protein STH1/NPS1 (2 entities in total)
• Functional Keywords: bromodomain, gene expression, chromatin structure, acetylated-lysine histone binding, gene regulation
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Total number of polymer chains: 6
• Total formula weight: 80117.95

Authors

Seo, H.S.,Hashimoto, H.,Krolak, A.,Debler, E.W.,Blus, B.J. (deposition date: 2018-10-11, release date: 2019-07-24, Last modification date: 2023-10-11)

Primary citation

Blus, B.J.,Hashimoto, H.,Seo, H.S.,Krolak, A.,Debler, E.W.
Substrate Affinity and Specificity of the ScSth1p Bromodomain Are Fine-Tuned for Versatile Histone Recognition.
Structure, 27:1460-1468.e3, 2019

PubMed Abstract: Bromodomains 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-Å 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.

PubMed: 31327661
DOI: 10.1016/j.str.2019.06.009

Experimental method

X-RAY DIFFRACTION (2.71 Å)