Structural insight into SUMO chain recognition and manipulation by the ubiquitin ligase RNF4

Xu, Yingqi; Plechanovová, Anna; Simpson, Peter; Marchant, Jan; Leidecker, Orsolya; Kraatz, S.H.W.; Hay, Ronald T.; Matthews, Stephen

doi:10.1038/ncomms5217

Cited by 41 publications

(91 citation statements)

References 57 publications

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“…Crystal structures of di‐ or tetra‐SUMOs should be regarded as snapshots that most likely do not represent the structure in solution. Indeed, NMR spectroscopy studies suggested high mobility for the SUMO subunits; however, it is not known if certain preferred conformations exist and how these are populated . Our ensemble FRET measurements report on the average of all of these possible conformations, and a conformation with the two fluorophores in close distance might dominate the overall FRET effect.…”

Section: Resultsmentioning

confidence: 87%

“…They are connected by flexible linkers of about six and five residues at their N‐ and C‐terminal ends, respectively. This view is supported by crystal structures of defined SUMO‐2 di‐ and tetramers that display no detectable electron density for the linker region, as well as by NMR spectroscopy and small‐angle X‐ray scattering (SAXS) experiments . The binding of multi‐SIM ligands of RNF4 to SUMO‐2 di‐ and tetramers has been investigated by the same studies by means of NMR spectroscopy and SAXS, and represent the only structural studies for such complexes so far.…”

Section: Introductionmentioning

confidence: 91%

“…Xu et al. determined the structure of the RNF4 SIM2/3 peptide with a SUMO‐2 dimer by NMR spectroscopy (PDB ID: 2MP2) . In two possible structures, SIM‐2 always bound in a parallel fashion, whereas SIM3 always bound in an antiparallel mode.…”

Section: Introductionmentioning

confidence: 99%

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A FRET Sensor to Monitor Bivalent SUMO–SIM Interactions in SUMO Chain Binding

Kost

Mootz

2017

ChemBioChem

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The small ubiquitin-like modifier (SUMO) can be assembled into polymeric chains as part of its diverse biochemical signal pattern upon conjugation to substrate proteins. SUMO chain recognition is facilitated by receptor proteins that contain at least two SUMO-interacting motifs (SIMs). Little is known about the structure of SUMO chains, both in an unliganded form and upon complexation with multi-SIM protein partners. A FRET sensor has been developed based on a linear dimer of human SUMO-2 as a minimal SUMO chain analogue. The synthetic acceptor and donor dyes were conjugated by maleimide and copper-catalyzed click chemistry to each of the two SUMO subunits. FRET changes were only observed in the presence of di- or multi-SIM ligands. Alteration of the short linker sequence between SIMs 2 and 3 of RNF4 showed a great tolerance, and hence, structural flexibility, of the SUMO dimer for bivalent binding of adjacent SIMs. The di-SUMO FRET sensor reports on the binding of SIM clusters of the proteins C5orf25 and SOBP; this suggest that these can bind to adjacent subunits of a SUMO chain. The developed FRET sensor will be a useful tool to study the importance of SIM and linker sequences, as well as biochemical and structural properties of SUMO chains and multi-SIM proteins.

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Section: Resultsmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 91%

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A FRET Sensor to Monitor Bivalent SUMO–SIM Interactions in SUMO Chain Binding

Kost

Mootz

2017

ChemBioChem

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“…STUbLs bind poly-SUMO chains noncovalently through their multiple SUMO interaction motifs (SIMs), which mediate their dimerization, a feature essential for their activity and the eventual polyubiquitination of both SUMO and its attached targets ( Fig. 1; Plechanovová et al, 2012;Xu et al, 2014). These polyubiquitinated proteins are then targeted for degradation by the ubiquitin-proteasome system ( Fig.…”

Section: The Sumo Conjugation and Deconjugation Systemmentioning

confidence: 99%

Analysis of Small Ubiquitin-Like Modifier (SUMO) Targets Reflects the Essential Nature of Protein SUMOylation and Provides Insight to Elucidate the Role of SUMO in Plant Development

Elrouby

2015

Plant Physiology

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Posttranslational modification of proteins by small ubiquitin-like modifier (SUMO) has received much attention, reflected by a flood of recent studies implicating SUMO in a wide range of cellular and molecular activities, many of which are conserved throughout eukaryotes. Whereas most of these studies were performed in vitro or in single cells, plants provide an excellent system to study the role of SUMO at the developmental level. Consistent with its essential roles during plant development, mutations of the basic SUMOylation machinery in Arabidopsis (Arabidopsis thaliana) cause embryo stage arrest or major developmental defects due to perturbation of the dynamics of target SUMOylation. Efforts to identify SUMO protein targets in Arabidopsis have been modest; however, recent success in identifying thousands of human SUMO targets using unique experimental designs can potentially help identify plant SUMO targets more efficiently. Here, known Arabidopsis SUMO targets are reevaluated, and potential approaches to dissect the roles of SUMO in plant development are discussed.

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“…2a) [33,34]. These interactions are characterized by backbone hydrogen bonds to positions 33, 35, and 37 to primarily β-strand motifs (Figs.…”

Section: Introductionmentioning

confidence: 99%

UbSRD: The Ubiquitin Structural Relational Database

Harrison

Jacobs

Houlihan

et al. 2016

Journal of Molecular Biology

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The structurally defined ubiquitin-like homology fold (UBL) can engage in several unique protein–protein interactions and many of these complexes have been characterized with high-resolution techniques. Using Rosetta's structural classification tools, we have created the Ubiquitin Structural Relational Database (UbSRD), an SQL database of features for all 509 UBL-containing structures in the PDB, allowing users to browse these structures by protein–protein interaction and providing a platform for quantitative analysis of structural features. We used UbSRD to define the recognition features of ubiquitin (UBQ) and SUMO observed in the PDB and the orientation of the UBQ tail while interacting with certain types of proteins. While some of the interaction surfaces on UBQ and SUMO overlap, each molecule has distinct features that aid in molecular discrimination. Additionally, we find that the UBQ tail is malleable and can adopt a variety of conformations upon binding. UbSRD is accessible as an online resource at rosettadesign.med.unc.edu/ubsrd.

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Structural insight into SUMO chain recognition and manipulation by the ubiquitin ligase RNF4

Cited by 41 publications

References 57 publications

A FRET Sensor to Monitor Bivalent SUMO–SIM Interactions in SUMO Chain Binding

A FRET Sensor to Monitor Bivalent SUMO–SIM Interactions in SUMO Chain Binding

Analysis of Small Ubiquitin-Like Modifier (SUMO) Targets Reflects the Essential Nature of Protein SUMOylation and Provides Insight to Elucidate the Role of SUMO in Plant Development

UbSRD: The Ubiquitin Structural Relational Database

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