The small ubiquitin-like modifier (SUMO) is a post-translational modifier that can regulate the function of hundreds of proteins inside the cell. SUMO belongs to the ubiquitin-like family of proteins that can be attached to target proteins by a dedicated enzymatic cascade pathway formed by E1, E2 and E3 enzymes. SUMOylation is involved in many cellular pathways, having in most instances essential roles for their correct function. In this review, we want to highlight the latest research on the molecular mechanisms that lead to the formation of the isopeptidic bond between the lysine substrate and the C-terminus of SUMO. In particular, we will focus on the recent discoveries on the catalytic function of the SUMO E3 ligases revealed by structural and biochemical approaches. Also, we will discuss important questions regarding specificity in SUMO conjugation, which it still remains as a major issue due to the small number of SUMO E3 ligases discovered so far, in contrast with the large number of SUMO conjugated proteins in the cell.
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Cover Image
Cover Image
The cover image depicts a combination of a 3D reconstruction of ER-TGN contact sites by focus ion beam-scanning electron microscopy (FIB-SEM) and five images showing the visualization of the contacts by FRET/FLIM. The 3D reconstruction of the Golgi stack was generated from FIB-SEM tomography of a HepG2 cell using IMOD software. The ER cisterna is shown in red (with ribosomes as white circles), while the trans-most cisterna of the Golgi stack is shown in green (with emerging clathrin-coated buds decorated by pink dots). The five FLIM images are from HeLa cells expressing a TGN reporter (TGN46-GFP) and an ER reporter (mCherry-Cb5). The pseudocolour scale represents donor (i.e. GFP) lifetime (τ) values ranging from 1.8 (blue) to 2.7 ns (red) under conditions that destabilize (left) or stabilize ER-TGN contact sites. For further information, see the review by Venditti and colleagues (pp. 187–197). Image courtesy of Maria Antonietta De Matteis.
Molecular mechanisms in SUMO conjugation
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