Identification of a SUMO-Binding Motif That Recognizes SUMO-Modified Proteins

• Published in: Proceedings of the National Academy of Sciences - PNAS 2004-10, Vol.101 (40), p.14373-14378
• Main Authors: Song, Jing, Durrin, Linda K., Wilkinson, Thomas A., Krontiris, Theodore G., Chen, Yuan, Varshavsky, Alexander
• Format: Article
• Language: English
• Subjects: Addition; Amino Acid Motifs; Amino Acid Sequence; Amino acids; Binding Sites; Biochemistry; Biological Sciences; Cellular biology; Chemical equilibrium; Consensus Sequence; Enzymes; GTPase-Activating Proteins - chemistry; GTPase-Activating Proteins - metabolism; Humans; In Vitro Techniques; Macromolecular Substances; Models, Molecular; Molecular Chaperones; Molecular Sequence Data; Mutagenesis, Site-Directed; Nuclear interactions; Nuclear Magnetic Resonance, Biomolecular; Nuclear Pore Complex Proteins - chemistry; Nuclear Pore Complex Proteins - metabolism; Post translational modification; Protein Processing, Post-Translational; Proteins; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Small Ubiquitin-Related Modifier Proteins - chemistry; Small Ubiquitin-Related Modifier Proteins - metabolism; Spectroscopy; Static Electricity; SUMO-1 Protein - chemistry; SUMO-1 Protein - metabolism; Ubiquitins
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0403498101

Posttranslational modification by the ubiquitin homologue, small ubiquitin-like modifier 1 (SUMO-1), has been established as an important regulatory mechanism. However, in most cases it is not clear how sumoylation regulates various cellular functions. Emerging evidence suggests that sumoylation may play a general role in regulating protein-protein interactions, as shown in RanBP2/Nup358 and RanGAP1 interaction. In this study, we have defined an amino acid sequence motif that binds SUMO. This motif, V/I-X-V/I-V/I, was identified by NMR spectroscopic characterization of interactions among SUMO-1 and peptides derived from proteins that are known to bind SUMO or sumoylated proteins. This motif binds all SUMO paralogues (SUMO-1-3). Using site-directed mutagenesis, we also show that this SUMO-binding motif in RanBP2/Nup358 is responsible for the interaction between RanBP2/Nup358 and sumoylated RanGAP1. The SUMO-binding motif exists in nearly all proteins known to be involved in SUMO-dependent processes, suggesting its general role in sumoylation-dependent cellular functions.