Potential 14-3-3 binding sites in sirtuins reveal extended phosphosite-recognition modes

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Weyand, Michael ; Quast, Laura ; Steegborn, Clemens:
Potential 14-3-3 binding sites in sirtuins reveal extended phosphosite-recognition modes.
In: Acta Crystallographica Section F. Bd. 82 (2026) Heft 1 . - S. 32-40.
ISSN 2053-230X
DOI: https://doi.org/10.1107/S2053230X25010908

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Abstract

The adapter proteins of the 14-3-3 family modulate the activity and/or localization of their binding partners, which they capture if a generic target motif is in its phosphorylated state. Here, we report the identification of potential 14-3-3 binding sites in human sirtuin deacylases by bioinformatic analysis. We then characterize the interactions of peptides representing phosphorylation sites in sirtuin 3 (pS103) and sirtuin 1 (pS670) with 14-3-3 proteins. We further describe the crystal structures of complexes of 14-3-3σ with either of the two phosphopeptides. As a conclusion, we propose a more extended 14-3-3 binding mode on the N-terminal side of the phosphorylation site and the possibility of nongeneric motifs and conformations on the C-terminal side, still resulting in the known high binding affinity of the two partners.