Structural and Functional Characterization of the Phosphorylation-Dependent Interaction between PML and SUMO1

• Published in: Structure (London) Vol. 23; no. 1; pp. 126 - 138
• Main Authors: Cappadocia, Laurent, Mascle, Xavier H., Bourdeau, Véronique, Tremblay-Belzile, Samuel, Chaker-Margot, Malik, Lussier-Price, Mathieu, Wada, Junya, Sakaguchi, Kazuyasu, Aubry, Muriel, Ferbeyre, Gerardo, Omichinski, James G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 06-01-2015; Elsevier
• Subjects: Adaptor Proteins, Signal Transducing - chemistry; Adaptor Proteins, Signal Transducing - metabolism; Amino Acid Sequence; Crystallography, X-Ray; HEK293 Cells; Humans; Models, Molecular; Molecular Sequence Data; Nuclear Proteins - chemistry; Nuclear Proteins - metabolism; Phosphorylation; Promyelocytic Leukemia Protein; Protein Binding; Protein Interaction Domains and Motifs; Protein Structure, Tertiary; Sequence Homology, Amino Acid; SUMO-1 Protein - chemistry; SUMO-1 Protein - metabolism; Transcription Factors - chemistry; Transcription Factors - metabolism; Tumor Suppressor Proteins - chemistry; Tumor Suppressor Proteins - metabolism
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2014.10.015

PML and several other proteins localizing in PML-nuclear bodies (PML-NB) contain phosphoSIMs (SUMO-interacting motifs), and phosphorylation of this motif plays a key role in their interaction with SUMO family proteins. We examined the role that phosphorylation plays in the binding of the phosphoSIMs of PML and Daxx to SUMO1 at the atomic level. The crystal structures of SUMO1 bound to unphosphorylated and tetraphosphorylated PML-SIM peptides indicate that three phosphoserines directly contact specific positively charged residues of SUMO1. Surprisingly, the crystal structure of SUMO1 bound to a diphosphorylated Daxx-SIM peptide indicate that the hydrophobic residues of the phosphoSIM bind in a manner similar to that seen with PML, but important differences are observed when comparing the phosphorylated residues. Together, the results provide an atomic level description of how specific acetylation patterns within different SUMO family proteins can work together with phosphorylation of phosphoSIM’s regions of target proteins to regulate binding specificity.
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•The structure of the phosphorylated SIM of PML in complex with SUMO1 is presented•Three phosphoserines in the SIM of PML play a key role in binding to SUMO1•K39, H43, and K46 of SUMO1 make specific contacts with the three phosphoserines•The phosphorylated SIM of Daxx in complex with SUMO1 differs from the SIM of PML
Phosphorylation of regions adjacent to SUMO-interacting motifs (SIMs) enhances their interactions with SUMO proteins. Cappadocia et al. have determined the structures of the phosphorylated SIMs of PML and Daxx bound to SUMO1 and show how key residues in SUMO proteins regulate interaction with phosphorylated SIMs.