@article{moreno-yruela_structural_2025,
	title = {Structural basis of {SIRT}7 nucleosome engagement and substrate specificity},
	volume = {16},
	issn = {2041-1723},
	url = {https://www.nature.com/articles/s41467-025-56529-y},
	doi = {10.1038/s41467-025-56529-y},
	abstract = {Abstract
            
              Chromatin-modifying enzymes target distinct residues within histones to finetune gene expression profiles. {SIRT}7 is an {NAD}
              +
              -dependent deacylase often deregulated in cancer, which deacetylates either H3 lysine 36 (H3K36) or H3K18 with high specificity within nucleosomes. Here, we report structures of nucleosome-bound {SIRT}7, and uncover the structural basis of its specificity towards H3K36 and K18 deacylation, combining a mechanism-based cross-linking strategy, cryo-{EM}, and enzymatic and cellular assays. We show that the {SIRT}7 N-terminus represents a unique, extended nucleosome-binding domain, reaching across the nucleosomal surface to the acidic patch. The catalytic domain binds at the H3-tail exit site, engaging both {DNA} gyres of the nucleosome. Contacting H3K36 versus H3K18 requires a change in binding pose, and results in structural changes in both {SIRT}7 and the nucleosome. These structures reveal the basis of lysine specificity, allowing us to engineer {SIRT}7 towards enhanced H3K18ac selectivity, and provides a basis for small molecule modulator development.},
	pages = {1328},
	number = {1},
	journaltitle = {Nature Communications},
	shortjournal = {Nat Commun},
	author = {Moreno-Yruela, Carlos and Ekundayo, Babatunde E. and Foteva, Polina N. and Ni, Dongchun and Calvino-Sanles, Esther and Stahlberg, Henning and Fierz, Beat},
	urldate = {2025-02-07},
	date = {2025-02-04},
	langid = {english},
}