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Using Cross‐Correlated Spin Relaxation to Characterize Backbone Dihedral Angle Distributions of Flexible Protein Segments
Crucial to the function of proteins is their existence as conformational ensembles sampling numerous and structurally diverse substates. Despite this widely accepted notion there is still a high demand for meaningful and reliable approaches to characterize protein ensembles in solution. As it is usu...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839595/ https://www.ncbi.nlm.nih.gov/pubmed/33119214 http://dx.doi.org/10.1002/cphc.202000789 |
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author | Kauffmann, Clemens Zawadzka‐Kazimierczuk, Anna Kontaxis, Georg Konrat, Robert |
author_facet | Kauffmann, Clemens Zawadzka‐Kazimierczuk, Anna Kontaxis, Georg Konrat, Robert |
author_sort | Kauffmann, Clemens |
collection | PubMed |
description | Crucial to the function of proteins is their existence as conformational ensembles sampling numerous and structurally diverse substates. Despite this widely accepted notion there is still a high demand for meaningful and reliable approaches to characterize protein ensembles in solution. As it is usually conducted in solution, NMR spectroscopy offers unique possibilities to address this challenge. Particularly, cross‐correlated relaxation (CCR) effects have long been established to encode both protein structure and dynamics in a compelling manner. However, this wealth of information often limits their use in practice as structure and dynamics might prove difficult to disentangle. Using a modern Maximum Entropy (MaxEnt) reweighting approach to interpret CCR rates of Ubiquitin, we demonstrate that these uncertainties do not necessarily impair resolving CCR‐encoded structural information. Instead, a suitable balance between complementary CCR experiments and prior information is found to be the most crucial factor in mapping backbone dihedral angle distributions. Experimental and systematic deviations such as oversimplified dynamics appear to be of minor importance. Using Ubiquitin as an example, we demonstrate that CCR rates are capable of characterizing rigid and flexible residues alike, indicating their unharnessed potential in studying disordered proteins. |
format | Online Article Text |
id | pubmed-7839595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78395952021-02-01 Using Cross‐Correlated Spin Relaxation to Characterize Backbone Dihedral Angle Distributions of Flexible Protein Segments Kauffmann, Clemens Zawadzka‐Kazimierczuk, Anna Kontaxis, Georg Konrat, Robert Chemphyschem Articles Crucial to the function of proteins is their existence as conformational ensembles sampling numerous and structurally diverse substates. Despite this widely accepted notion there is still a high demand for meaningful and reliable approaches to characterize protein ensembles in solution. As it is usually conducted in solution, NMR spectroscopy offers unique possibilities to address this challenge. Particularly, cross‐correlated relaxation (CCR) effects have long been established to encode both protein structure and dynamics in a compelling manner. However, this wealth of information often limits their use in practice as structure and dynamics might prove difficult to disentangle. Using a modern Maximum Entropy (MaxEnt) reweighting approach to interpret CCR rates of Ubiquitin, we demonstrate that these uncertainties do not necessarily impair resolving CCR‐encoded structural information. Instead, a suitable balance between complementary CCR experiments and prior information is found to be the most crucial factor in mapping backbone dihedral angle distributions. Experimental and systematic deviations such as oversimplified dynamics appear to be of minor importance. Using Ubiquitin as an example, we demonstrate that CCR rates are capable of characterizing rigid and flexible residues alike, indicating their unharnessed potential in studying disordered proteins. John Wiley and Sons Inc. 2020-12-10 2021-01-07 /pmc/articles/PMC7839595/ /pubmed/33119214 http://dx.doi.org/10.1002/cphc.202000789 Text en © 2020 The Authors. ChemPhysChem published by Wiley-VCH GmbH This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Kauffmann, Clemens Zawadzka‐Kazimierczuk, Anna Kontaxis, Georg Konrat, Robert Using Cross‐Correlated Spin Relaxation to Characterize Backbone Dihedral Angle Distributions of Flexible Protein Segments |
title | Using Cross‐Correlated Spin Relaxation to Characterize Backbone Dihedral Angle Distributions of Flexible Protein Segments |
title_full | Using Cross‐Correlated Spin Relaxation to Characterize Backbone Dihedral Angle Distributions of Flexible Protein Segments |
title_fullStr | Using Cross‐Correlated Spin Relaxation to Characterize Backbone Dihedral Angle Distributions of Flexible Protein Segments |
title_full_unstemmed | Using Cross‐Correlated Spin Relaxation to Characterize Backbone Dihedral Angle Distributions of Flexible Protein Segments |
title_short | Using Cross‐Correlated Spin Relaxation to Characterize Backbone Dihedral Angle Distributions of Flexible Protein Segments |
title_sort | using cross‐correlated spin relaxation to characterize backbone dihedral angle distributions of flexible protein segments |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839595/ https://www.ncbi.nlm.nih.gov/pubmed/33119214 http://dx.doi.org/10.1002/cphc.202000789 |
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