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Sequence-Specific Mapping of the Interaction between Urea and Unfolded Ubiquitin from Ensemble Analysis of NMR and Small Angle Scattering Data

Huang, Jie-Rong and Gabel, Frank and Jensen, Malene Ringkjøbing and Grzesiek, Stephan and Blackledge, Martin. (2012) Sequence-Specific Mapping of the Interaction between Urea and Unfolded Ubiquitin from Ensemble Analysis of NMR and Small Angle Scattering Data. Journal of the American Chemical Society, Vol. 134, H. 9. pp. 4429-4436.

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Official URL: http://edoc.unibas.ch/dok/A6002481

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Abstract

The molecular details of how urea interacts with, and eventually denatures proteins, remain largely unknown. In this study we have used extensive experimental NMR data, in combination with statistical coil ensemble modelling and small angle scattering, to analyze the conformational behavior of the protein ubiquitin in the presence of urea. In order to develop an atomic resolution understanding of the denatured state, conformational ensembles of full-atom descriptions of unfolded proteins, including sidechain conformations derived from rotamer libraries, are combined with random sampling of explicit urea molecules in interaction with the protein. Using this description of the conformational equilibrium, we demonstrate that the direct-binding model of urea to the protein backbone is compatible with available experimental data. We find that in the presence of 8M urea, between 30 and 40% of the backbone peptide groups bind a urea molecule, independently reproducing results from a model-free analysis of small angle neutron and X-ray scattering data. Crucially, this analysis provides sequence specific details of the interaction between urea and the protein backbone. The pattern of urea-binding along the amino-acid sequence reveals a higher level of binding in the central part of the protein, a trend which resembles independent results derived from chemical shift mapping of the urea-protein interaction. Together these results substantiate the direct-binding model and provide a framework for studying the physical basis of interactions between proteins and solvent molecules.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Grzesiek)
UniBasel Contributors:Grzesiek, Stephan
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Chemical Society
ISSN:0002-7863
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:11 Oct 2012 15:31
Deposited On:11 Oct 2012 15:19

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