EurekaMag.com logo
+ Site Statistics
References:
53,517,315
Abstracts:
29,339,501
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Unique binding interactions among Ubc9, SUMO and RanBP2 reveal a mechanism for SUMO paralog selection



Unique binding interactions among Ubc9, SUMO and RanBP2 reveal a mechanism for SUMO paralog selection



Nature Structural & Molecular Biology 12(1): 67-74



The conjugation of small ubiquitin-like modifiers SUMO-1, SUMO-2 and SUMO-3 onto target proteins requires the concerted action of the specific E1-activating enzyme SAE1/SAE2, the E2-conjugating enzyme Ubc9, and an E3-like SUMO ligase. NMR chemical shift perturbation was used to identify the surface of Ubc9 that interacts with the SUMO ligase RanBP2. Unlike known ubiquitin E2-E3 interactions, RanBP2 binds to the beta-sheet of Ubc9. Mutational disruption of Ubc9-RanBP2 binding affected SUMO-2 but not SUMO-1 conjugation to Sp100 and to a newly identified RanBP2 substrate, PML. RanBP2 contains a binding site specific for SUMO-1 but not SUMO-2, indicating that a Ubc9-SUMO-1 thioester could be recruited to RanBP2 via SUMO-1 in the absence of strong binding between Ubc9 and RanBP2. Thus we show that E2-E3 interactions are not conserved across the ubiquitin-like protein superfamily and identify a RanBP2-dependent mechanism for SUMO paralog-specific conjugation.

(PDF same-day service: $19.90)

Accession: 012722700

Download citation: RISBibTeXText

PMID: 15608651

DOI: 10.1038/nsmb878



Related references

The Mdm-2 amino terminus is required for Mdm2 binding and SUMO-1 conjugation by the E2 SUMO-1 conjugating enzyme Ubc9. Journal of Biological Chemistry 276(44): 40389-40395, 2001

The small ubiquitin-like modifier-1 (SUMO-1) consensus sequence mediates Ubc9 binding and is essential for SUMO-1 modification. Journal of Biological Chemistry 276(24): 21664-9, 2001

Small ubiquitin-related modifier (SUMO) binding determines substrate recognition and paralog-selective SUMO modification. Journal of Biological Chemistry 283(43): 29405-29415, 2008

The RanBP2/RanGAP1*SUMO1/Ubc9 complex is a multisubunit SUMO E3 ligase. Molecular Cell 46(3): 287-298, 2012

Enhanced SUMOylation of proteins containing a SUMO-interacting motif by SUMO-Ubc9 fusion. Biochemical and Biophysical Research Communications 388(1): 41-45, 2009

Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. Journal of Biological Chemistry 276(38): 35368-35374, 2001

Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1. Biochemical and Biophysical Research Communications 289(4): 862-868, 2001

SUMO and SUMO-Conjugating Enzyme E2 UBC9 Are Involved in White Spot Syndrome Virus Infection in Fenneropenaeus chinensis. Plos One 11(2): E0150324-E0150324, 2016

Modification of CCAAT/Enhancer-binding Protein-b by the Small Ubiquitin-like Modifier (SUMO) Family Members, SUMO-2 and SUMO-3. The Journal of Biological Chemistry 278(35): 416-21, 2003

Modification of CCAAT/enhancer-binding protein-beta by the small ubiquitin-like modifier (SUMO) family members, SUMO-2 and SUMO-3. Journal of Biological Chemistry 278(35): 33416-33421, 2003

Fourier transform ion cyclotron resonance mass spectrometry for the analysis of small ubiquitin-like modifier (SUMO) modification: identification of lysines in RanBP2 and SUMO targeted for modification during the E3 autoSUMOylation reaction. Analytical Chemistry 77(19): 6310-6319, 2005

Structure of a SUMO-binding-motif mimic bound to Smt3p-Ubc9p: conservation of a non-covalent ubiquitin-like protein-E2 complex as a platform for selective interactions within a SUMO pathway. Journal of Molecular Biology 369(3): 619-630, 2007

Crystal structure of UBA2(ufd)-Ubc9: insights into E1-E2 interactions in Sumo pathways. Plos One 5(12): E15805-E15805, 2011

Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation. Biochemistry 42(33): 9959-9969, 2003