Characterization of a C-Terminal SUMO-Interacting Motif Present in Select PIAS-Family Proteins

Structure. 2020 May 5;28(5):573-585.e5. doi: 10.1016/j.str.2020.04.002. Epub 2020 Apr 28.


The human PIAS proteins are small ubiquitin-like modifier (SUMO) E3 ligases that participate in important cellular functions. Several of these functions depend on a conserved SUMO-interacting motif (SIM) located in the central region of all PIAS proteins (SIM1). Recently, it was determined that Siz2, a yeast homolog of PIAS proteins, possesses a second SIM at its C terminus (SIM2). Sequence alignment indicates that a SIM2 is also present in PIAS1-3, but not PIAS4. Using biochemical and structural studies, we demonstrate PIAS-SIM2 binds to SUMO1, but that phosphorylation of the PIAS-SIM2 or acetylation of SUMO1 alter this interaction in a manner distinct from what is observed for the PIAS-SIM1. We also show that the PIAS-SIM2 plays a key role in formation of a UBC9-PIAS1-SUMO1 complex. These results provide insights into how post-translational modifications selectively regulate the specificity of multiple SIMs found in the PIAS proteins by exploiting the plasticity built into the SUMO-SIM binding interface.

Keywords: BRET; ITC; Mre11; PIAS-family proteins; SUMO; SUMO-interacting motif; Siz2; acetylation; crystallography; phosphorylation.

Publication types

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

MeSH terms

  • Acetylation
  • Amino Acid Motifs
  • Crystallography, X-Ray
  • HEK293 Cells
  • Humans
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Phosphorylation
  • Poly-ADP-Ribose Binding Proteins / chemistry
  • Poly-ADP-Ribose Binding Proteins / genetics
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • Protein Inhibitors of Activated STAT / chemistry*
  • Protein Inhibitors of Activated STAT / genetics
  • Protein Inhibitors of Activated STAT / metabolism*
  • Protein Interaction Domains and Motifs
  • SUMO-1 Protein / metabolism*
  • Serine / metabolism
  • Small Ubiquitin-Related Modifier Proteins / chemistry
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Ubiquitin-Conjugating Enzymes / metabolism


  • Molecular Chaperones
  • Multiprotein Complexes
  • PIAS1 protein, human
  • PIAS2 protein, human
  • PIAS3 protein, human
  • PIAS4 protein, human
  • Poly-ADP-Ribose Binding Proteins
  • Protein Inhibitors of Activated STAT
  • SUMO-1 Protein
  • SUMO1 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Serine
  • Ubiquitin-Conjugating Enzymes
  • ubiquitin-conjugating enzyme UBC9