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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

Diehl, Carl LU ; Akke, Mikael LU orcid ; Bekker-Jensen, Simon ; Mailand, Niels ; Streicher, Werner and Wikström, Mats (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
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organization
publishing date
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}},
}