Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex Journal Article
| Authors: | Reverter, D.; Lima, C. D. |
| Article Title: | Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex |
| Abstract: | SUMO-1 (for small ubiquitin-related modifier) belongs to the ubiquitin (Ub) and ubiquitin-like (Ubl) protein family. SUMO conjugation occurs on specific lysine residues within protein targets, regulating pathways involved in differentiation, apoptosis, the cell cycle and responses to stress by altering protein function through changes in activity or cellular localization or by protecting substrates from ubiquitination. Ub/Ubl conjugation occurs in sequential steps and requires the concerted action of E2 conjugating proteins and E3 ligases. In addition to being a SUMO E3, the nucleoporin Nup358/RanBP2 localizes SUMO-conjugated RanGAP1 to the cytoplasmic face of the nuclear pore complex by means of interactions in a complex that also includes Ubc9, the SUMO E2 conjugating protein. Here we describe the 3.0-Å crystal structure of a four-protein complex of Ubc9, a Nup358/RanBP2 E3 ligase domain (IR1-M) and SUMO-1 conjugated to the carboxy-terminal domain of RanGAPl. Structural insights, combined with biochemical and kinetic data obtained with additional substrates, support a model in which Nup358/RanBP2 acts as an E3 by binding both SUMO and Ubc9 to position the SUMO-E2-thioester in an optimal orientation to enhance conjugation. |
| Keywords: | unclassified drug; molecular genetics; ubiquitin; protein conformation; protein domain; protein function; protein localization; metabolism; cell cycle; complex formation; apoptosis; ubiquitin protein ligase; carboxy terminal sequence; protein; protein interaction; enzyme activity; structure activity relation; structure-activity relationship; chemistry; ubiquitination; amino acid sequence; molecular sequence data; kinetics; guanosine triphosphatase activating protein; binding site; gtpase-activating proteins; stress; crystal structure; models, molecular; crystallography, x-ray; multiprotein complexes; binding sites; chemical structure; x ray crystallography; ubiquitin protein ligase e3; sumo protein; sumo-1 protein; ubiquitin-conjugating enzymes; biochemistry; medicine; ubiquitin-protein ligases; enzyme localization; enzymes; lysine; thioester; substrates; differentiation; ubiquitin conjugating enzyme; nuclear pore complex proteins; chaperone; conjugation; cells; multiprotein complex; sumo 1 protein; molecular chaperones; exportin 5; mathematical models; nucleoporin; nuclear pore complex; protein ubc9; ubiquitin conjugating enzyme ubc9; ubiquitin-conjugating enzyme ubc9; ran binding protein 2; natural sciences; stress analysis; biochemical data; regulating pathways; ubiquitin (ub); e2 conjugating protein; nucleoporin 358; rangap1 protein; ubiquitin 1; ran-binding protein 2; rangap1 protein, human |
| Journal Title: | Nature |
| Volume: | 435 |
| Issue: | 7042 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2005-06-02 |
| Start Page: | 687 |
| End Page: | 692 |
| Language: | English |
| DOI: | 10.1038/nature03588 |
| PUBMED: | 15931224 |
| PROVIDER: | scopus |
| PMCID: | PMC1416492 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 178" - "Export Date: 24 October 2012" - "CODEN: NATUA" - "Source: Scopus" |
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