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

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

doi:10.1016/j.str.2020.04.002

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.

Authors

Mathieu Lussier-Price¹, Xavier H Mascle¹, Laurent Cappadocia¹, Rui Kamada², Kazuyasu Sakaguchi², Haytham M Wahba³, 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 Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan.
³ Département de Biochimie et Médicine Moléculaire, Université de Montréal, C.P. 6128 Succursale Centre-Ville, Montréal, QC H3C 3J7, Canada; Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan; Department of Biochemistry, Beni-Suef University, Beni-Suef 62521, Egypt.
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: 32348746
DOI: 10.1016/j.str.2020.04.002

Abstract

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

Substances

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