Structural analysis of a complex between small ubiquitin-like modifier 1 (SUMO1) and the ZZ domain of CREB-binding protein (CBP/p300) reveals a new interaction surface on SUMO
(2016) In Journal of Biological Chemistry 291(24). p.12658-12672- Abstract
We have recently discovered that the ZZ zinc finger domain represents a novel small ubiquitin-like modifier (SUMO) binding motif. In this study we identify the binding epitopes in the ZZ domain of CBP (CREB-binding protein) and SUMO1 using NMR spectroscopy. The binding site on SUMO1 represents a unique epitope for SUMO interaction spatially opposite to that observed for canonical SUMO interaction motifs (SIMs). HADDOCK docking simulations using chemical shift perturbations and residual dipolar couplings was employed to obtain a structural model for the ZZ domain-SUMO1 complex. Isothermal titration calorimetry experiments support this model by showing that the mutation of key residues in the binding site abolishes binding and that SUMO1... (More)
We have recently discovered that the ZZ zinc finger domain represents a novel small ubiquitin-like modifier (SUMO) binding motif. In this study we identify the binding epitopes in the ZZ domain of CBP (CREB-binding protein) and SUMO1 using NMR spectroscopy. The binding site on SUMO1 represents a unique epitope for SUMO interaction spatially opposite to that observed for canonical SUMO interaction motifs (SIMs). HADDOCK docking simulations using chemical shift perturbations and residual dipolar couplings was employed to obtain a structural model for the ZZ domain-SUMO1 complex. Isothermal titration calorimetry experiments support this model by showing that the mutation of key residues in the binding site abolishes binding and that SUMO1 can simultaneously and noncooperatively bind both the ZZ domain and a canonical SIM motif. The binding dynamics of SUMO1 was further characterized using 15N Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersions, which define the off rates for the ZZ domain and SIM motif and show that the dynamic binding process has different characteristics for the two cases. Furthermore, in the absence of bound ligands SUMO1 transiently samples a high energy conformation, which might be involved in ligand binding.
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- author
- Diehl, Carl LU ; Akke, Mikael LU ; Bekker-Jensen, Simon ; Mailand, Niels ; Streicher, Werner and Wikström, Mats
- organization
- publishing date
- 2016-06-10
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 291
- issue
- 24
- pages
- 15 pages
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:27129204
- wos:000378119900021
- scopus:84974559357
- ISSN
- 0021-9258
- DOI
- 10.1074/jbc.M115.711325
- language
- English
- LU publication?
- yes
- id
- 39f89487-6986-4deb-a165-cd8def0b541c
- date added to LUP
- 2017-01-24 09:47:47
- date last changed
- 2024-05-18 20:01:53
@article{39f89487-6986-4deb-a165-cd8def0b541c, abstract = {{<p>We have recently discovered that the ZZ zinc finger domain represents a novel small ubiquitin-like modifier (SUMO) binding motif. In this study we identify the binding epitopes in the ZZ domain of CBP (CREB-binding protein) and SUMO1 using NMR spectroscopy. The binding site on SUMO1 represents a unique epitope for SUMO interaction spatially opposite to that observed for canonical SUMO interaction motifs (SIMs). HADDOCK docking simulations using chemical shift perturbations and residual dipolar couplings was employed to obtain a structural model for the ZZ domain-SUMO1 complex. Isothermal titration calorimetry experiments support this model by showing that the mutation of key residues in the binding site abolishes binding and that SUMO1 can simultaneously and noncooperatively bind both the ZZ domain and a canonical SIM motif. The binding dynamics of SUMO1 was further characterized using 15N Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersions, which define the off rates for the ZZ domain and SIM motif and show that the dynamic binding process has different characteristics for the two cases. Furthermore, in the absence of bound ligands SUMO1 transiently samples a high energy conformation, which might be involved in ligand binding.</p>}}, author = {{Diehl, Carl and Akke, Mikael and Bekker-Jensen, Simon and Mailand, Niels and Streicher, Werner and Wikström, Mats}}, issn = {{0021-9258}}, language = {{eng}}, month = {{06}}, number = {{24}}, pages = {{12658--12672}}, publisher = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Biological Chemistry}}, title = {{Structural analysis of a complex between small ubiquitin-like modifier 1 (SUMO1) and the ZZ domain of CREB-binding protein (CBP/p300) reveals a new interaction surface on SUMO}}, url = {{http://dx.doi.org/10.1074/jbc.M115.711325}}, doi = {{10.1074/jbc.M115.711325}}, volume = {{291}}, year = {{2016}}, }