SUMO

From Proteopedia

Revision as of 11:50, 28 December 2010

Template:STRUCTURE 1wm2

SUMO is a small ubiquitin-like modifier which covalently attaches to cellular proteins to modify their function. SUMO is similar in structure but not in sequence to ubiquitin. In several organisms SUMO is called SMT3. The SUMO-conjugating enzyme is called UBC9. The sentrin specific protease (SEPN) cleaves the C-terminal peptide from SUMO which then can bind to E1. The images at the left and at the right correspond to one representative SUMO, i.e. the crystal structure of human SUMO-2 protein (1wm2).

3D Structures of SUMO

SUMO

2k8h – SUMO – NMR – Trypanosoma brucei
1u4a – hSUMO-3 (mutant) – NMR – human
1a5r - hSUMO-1
1wm2, 1wm3, 2awt – hSUMO-2

SUMO+ubiquitin-like SUMO-conjugating enzyme

2vrr, 2uyz – mSUMO-1+UBC9
2pe6 - hSUMO-1+UBC9

SUMO+sentrin specific protease

2io0 – pre-hSUMO-2+SEPN2
2io1 - pre-hSUMO-3+SEPN2
2g4d - hSUMO-1+SEPN1
2iy1 - hSUMO-1+SEPN1 (mutant)
2iyd, 2ckh - hSUMO-2+SEPN1
1tgz - hSUMO-1+SEPN2
2io3 - pre-hSUMO-2+SEPN2 (mutant)+RAN GTPase-activating enzyme (mutant)
2iy0 - hSUMO-1+SEPN1 (mutant)+RAN GTPase-activating enzyme

SUMO+ubiquitin-conjugating enzyme

1z5s - hSUMO-1+E2+ RAN GTPase-activating enzyme
2bf8 - SUMO-1+E2 - bovine

SMT3

2k1f – SMT3 – Fruit fly
2eke – ySMT3+UBC9 – yeast
1euv – ySMT3+ULP1 protease

SUMO+other proteins

2asq – hSUMO-1+SUMO-binding motif in PIASX
3kyc, 3kyd – hSUMO+SUMO-activating enzyme
2rpq – hSUMO-3+activating transcription factor
1wyw - hSUMO-1+thymine DNA glycosylate
2d07 - hSUMO-3+thymine DNA glycosylate
2kqs - hSUMO-1+death domain-associated protein 6 fragment

Ubiquitin (Ub) and ubiquitin-like (Ubl) proteins attached to their target proteins and modulating the activities of those targets in various ways. Three types of evolutionarily conserved enzymes — E1 activating enzymes, E2 conjugating enzymes and E3 ligase enzymes — act sequentially through parallel yet distinct pathways to conjugate ubiquitin and Ubl proteins, such as SUMO and NEDD8, to their targets. The E1 enzyme uses the and magnesium to adenylate the C-terminal Ub/Ubl glycine, releasing pyrophosphate and resulting in . A non-hydrolysable and were constructed. In both these compounds the atom of phosphorus is replaced by sulfur (colored yellow).

The of the crystal structures for human SUMO E1 in complex with SUMO adenylate (AMSN) and tetrahedral intermediate (AVSN) analogues revealed opened conformation (SUMO1 in orange, SAE1 colored in blue, and other domains in darkviolet) and closed conformation (SUMO1 in yellow, SAE1 colored in cyan, and other domains in magenta), respectively. In the (3kyc) the distance between Cys domain (including Cys173) and mimic of the acyl adenylate intermediate AMSN is very long, while in the (3kyd), the catalytic Cys173 is posioned near AVSN and SUMO1, so the overall structure revealed dramatic rearrangement. This large conformational change forms the .

For better understanding of the difference between these two conformations you can see this morph (generated by using POLYVIEW-3D: http://polyview.cchmc.org/polyview3d.html; reload/refresh this page to restart this movie). Of note, in contrast to the previous figure, the same domains of these two structures (3kyc and 3kyd) are colored in the same colors (SUMO1 in yellow, SAE1 colored in blue and other domains in darkviolet). The catalytic Cys173 is shown in the spacefill representation and colored green, AMSN (or AVSN) are shown in the spacefill representation and colored in CPK colors.

Reference

• Olsen SK, Capili AD, Lu X, Tan DS, Lima CD. Active site remodelling accompanies thioester bond formation in the SUMO E1. Nature. 2010 Feb 18;463(7283):906-12. PMID:20164921 doi:10.1038/nature08765