Acetylation of SUMO1 Alters Interactions with the SIMs of PML and Daxx in a Protein-Specific Manner

The interactions between SUMO proteins and SUMO-interacting motif (SIM) in nuclear bodies formed by the promyelocytic leukemia (PML) protein (PML-NBs) have been shown to be modulated by either phosphorylation of the SIMs or acetylation of SUMO proteins. However, little is known about how this occurs at the atomic level. In this work, we examined the role that acetylation of SUMO1 plays on its binding to the phosphorylated SIMs (phosphoSIMs) of PML and Daxx. Our results demonstrate that SUMO1 binding to the phosphoSIM of either PML or Daxx is dramatically reduced by acetylation at either K39 or K46. However, acetylation at K37 only impacts binding to Daxx. Structures of acetylated SUMO1 variants bound to the phosphoSIMs of PML and Daxx demonstrate that there is structural plasticity in SUMO-SIM interactions. The plasticity observed in these structures provides a robust mechanism for regulating SUMO-SIM interactions in PML-NBs using signaling generated post-translational modifications. [Display omitted] •Structures of PML and Daxx phosphoSIMs bound to acetylated SUMO1 are presented•Acetylation of SUMO1 at key Lys residues alters interactions with the phosphoSIMs•SUMO1 acetylation at K39 or K46 inhibits binding to phosphoSIMs of PML and Daxx•SUMO1 acetylation at K37 inhibits binding only to the phosphoSIM of Daxx Mascle et al. describe structural details of how acetylation of SUMO1 at lysine residues in its SIM-binding region alters interactions with the phosphorylated SIMs of PML and Daxx. In particular, acetylation at K37 alters interaction with the Daxx-SIM, but not with the PML-SIM, which highlights the plasticity of SUMO-SIM interactions.