tailieunhanh - Báo cáo khoa học: Protein interactions in the sumoylation cascade – lessons from X-ray structures

Sumoylation is a multi-step protein modification reaction in which SUMO (small ubiquitin-like modifier) proteins are covalently attached to lysine res-idues of substrate proteins. Here, we compare the sequences and structures of modifiers and enzymes involved in sumoylation with those of the related ubiquitination and neddylation cascades. | IFEBS Journal REVIEW ARTICLE Protein interactions in the sumoylation cascade - lessons from X-ray structures Zhongshu Tang1 z Christina M. Hecker2 f Astrid Scheschonka1 and Heinrich Betz1 1 Department of Neurochemistry Max-Planck-Institute for Brain Research Frankfurt Germany 2 Department of Biochemistry II Johann-Wolfgang-Goethe-University University Hospital Frankfurt Germany Keywords Aos1-uba2 neddylation Pc2 PIAS proteins RanBP2 RanGAP1 SUMO sumoylation ubc9 ubiquitination Correspondence H. Betz Department of Neurochemistry Max-Planck-Institute for Brain Research Deutschordenstrasse 46 60528 Frankfurt Germany Fax 49 69 96769 441 Tel 49 69 96769 220 E-mail neurochemie@ Sumoylation is a multi-step protein modification reaction in which SUMO small ubiquitin-like modifier proteins are covalently attached to lysine residues of substrate proteins. Here we compare the sequences and structures of modifiers and enzymes involved in sumoylation with those of the related ubiquitination and neddylation cascades. By using available structural data on modifier enzyme substrate interactions we discuss and model sumoy-lation complexes that include SUMO-1 and the E1 and E2 enzymes Aos1-uba2 and ubc9 or SUMO-1 and E2 together with the E3 ligase RanBP2 and its substrate RanGAP1. Their comparison provides insight into the protein interactions underlying sumoylation and suggests how SUMO proteins may be translocated between enzymes during the various steps of the protein modification reaction. Present addresses NIH NEI Bethesda MD USA fDepartment of Systemic CellBiology Max-Planck-Institute for Molecular Physiology Dortmund Germany Received 21 November 2007 revised 20 March 2008 accepted 11 April 2008 doi Introduction Sumoylation is a post-translational modification in which a SUMO small ubiquitin-like modifier protein is conjugated to the e-amino group of a lysine residue of the substrate protein 1 2 . SUMO attachment has been .