2EKE

Structure of a SUMO-binding-motif mimic bound to Smt3p-Ubc9p: conservation of a noncovalent Ubiquitin-like protein-E2 complex as a platform for selective interactions within a SUMO pathway

Summary for 2EKE

• Entry DOI: 10.2210/pdb2eke/pdb
• Related: 1EUV 1WYW 1Z5S
• Descriptor: SUMO-conjugating enzyme UBC9, Ubiquitin-like protein SMT3 (3 entities in total)
• Functional Keywords: ubc9, smt3, sumo binding motif, sbm, ligase-protein binding complex, ligase/protein binding
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Cellular location: Nucleus: P50623
• Total number of polymer chains: 4
• Total formula weight: 60254.24

Authors

Duda, D.M.,Schulman, B.A. (deposition date: 2007-03-23, release date: 2007-05-29, Last modification date: 2023-10-25)

Primary citation

Duda, D.M.,van Waardenburg, R.C.A.M.,Borg, L.A.,McGarity, S.,Nourse, A.,Waddell, M.B.,Bjornsti, M.A.,Schulman, B.A.
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
J.Mol.Biol., 369:619-630, 2007

PubMed Abstract: The SUMO ubiquitin-like proteins play regulatory roles in cell division, transcription, DNA repair, and protein subcellular localization. Paralleling other ubiquitin-like proteins, SUMO proteins are proteolytically processed to maturity, conjugated to targets by E1-E2-E3 cascades, and subsequently recognized by specific downstream effectors containing a SUMO-binding motif (SBM). SUMO and its E2 from the budding yeast Saccharomyces cerevisiae, Smt3p and Ubc9p, are encoded by essential genes. Here we describe the 1.9 A resolution crystal structure of a non-covalent Smt3p-Ubc9p complex. Unexpectedly, a heterologous portion of the crystallized complex derived from the expression construct mimics an SBM, and binds Smt3p in a manner resembling SBM binding to human SUMO family members. In the complex, Smt3p binds a surface distal from Ubc9's catalytic cysteine. The structure implies that a single molecule of Smt3p cannot bind concurrently to both the non-covalent binding site and the catalytic cysteine of a single Ubc9p molecule. However, formation of higher-order complexes can occur, where a single Smt3p covalently linked to one Ubc9p's catalytic cysteine also binds non-covalently to another molecule of Ubc9p. Comparison with other structures from the SUMO pathway suggests that formation of the non-covalent Smt3p-Ubc9p complex occurs mutually exclusively with many other Smt3p and Ubc9p interactions in the conjugation cascade. By contrast, high-resolution insights into how Smt3p-Ubc9p can also interact with downstream recognition machineries come from contacts with the SBM mimic. Interestingly, the overall architecture of the Smt3p-Ubc9p complex is strikingly similar to recent structures from the ubiquitin pathway. The results imply that non-covalent ubiquitin-like protein-E2 complexes are conserved platforms, which function as parts of larger assemblies involved in many protein post-translational regulatory pathways.

PubMed: 17475278
DOI: 10.1016/j.jmb.2007.04.007

Experimental method

X-RAY DIFFRACTION (1.9 Å)