Peer review process
Not revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, and public reviews.
Read more about eLife’s peer review process.Editors
- Reviewing EditorTim FormosaUniversity of Utah School of Medicine, Salt Lake City, United States of America
- Senior EditorMerritt MadukeStanford University, Stanford, United States of America
Joint Public Review:
Smirnova et al. present a cryo-EM structure of human SIRT6 bound to a nucleosome as well as the results from molecular dynamics simulations. The results show that the combined conformational flexibilities of SIRT6 and the N-terminal tail of histone H3 limit the residues with access to the active site, partially explaining the substrate specificity of this sirtuin-class histone deacetylase. The cryo-EM analysis in its current form is incomplete, lacking aspects of validation such as angular distribution information and other standard measurements of the quality of the reconstruction. Biochemical validation of the structural findings is inadequate, relying primarily on previous publications. Importantly, two other groups have recently published cryo-EM structures of SIRT6:nucleosome complexes. This manuscript by Smirnova et al., therefore, confirms and complements these previous findings, with the addition of some novel insights into the role of structural flexibility in substrate selection.
