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

Xavier H Mascle; Christina Gagnon; Haytham M Wahba; Mathieu Lussier-Price; Laurent Cappadocia; Kazuyasu Sakaguchi; James G Omichinski

doi:10.1016/j.str.2019.11.019

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

Structure. 2020 Feb 4;28(2):157-168.e5. doi: 10.1016/j.str.2019.11.019. Epub 2019 Dec 23.

Authors

Xavier H Mascle¹, Christina Gagnon¹, Haytham M Wahba², Mathieu Lussier-Price¹, Laurent Cappadocia¹, Kazuyasu Sakaguchi³, James G Omichinski⁴

Affiliations

¹ Département de Biochimie et Médicine Moléculaire, Université de Montréal, C.P. 6128 Succursale Centre-Ville, Montréal, QC H3C 3J7, Canada.
² Département de Biochimie et Médicine Moléculaire, Université de Montréal, C.P. 6128 Succursale Centre-Ville, Montréal, QC H3C 3J7, Canada; Department of Biochemistry, Beni-Suef University, Beni-Suef 62521, Egypt.
³ Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan.
⁴ Département de Biochimie et Médicine Moléculaire, Université de Montréal, C.P. 6128 Succursale Centre-Ville, Montréal, QC H3C 3J7, Canada. Electronic address: jg.omichinski@umontreal.ca.

PMID: 31879127
DOI: 10.1016/j.str.2019.11.019

Abstract

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.

Keywords: BRET; Daxx; ITC; PML; PML nuclear bodies; SUMO; SUMO-interacting motif; acetylation; crystallography; phosphorylation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Acetylation
Binding Sites
Co-Repressor Proteins / chemistry*
Co-Repressor Proteins / metabolism*
Crystallography, X-Ray
HEK293 Cells
Humans
Lysine / metabolism
Models, Molecular
Molecular Chaperones / chemistry*
Molecular Chaperones / metabolism*
Mutation
Phosphorylation
Promyelocytic Leukemia Protein / chemistry*
Promyelocytic Leukemia Protein / metabolism*
Protein Binding
Protein Conformation
Protein Domains
Protein Folding
SUMO-1 Protein / chemistry*
SUMO-1 Protein / genetics
SUMO-1 Protein / metabolism*

Substances

Co-Repressor Proteins
DAXX protein, human
Molecular Chaperones
Promyelocytic Leukemia Protein
SUMO-1 Protein
SUMO1 protein, human
PML protein, human
Lysine