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Characterization of Weak Protein Domain Structure by Spin-Label Distance Distributions
Function of intrinsically disordered proteins may depend on deviation of their conformational ensemble from that of a random coil. Such deviation may be hard to characterize and quantify, if it is weak. We explored the potential of distance distributions between spin labels, as they can be measured...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072059/ https://www.ncbi.nlm.nih.gov/pubmed/33912586 http://dx.doi.org/10.3389/fmolb.2021.636599 |
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author | Ritsch, Irina Esteban-Hofer, Laura Lehmann, Elisabeth Emmanouilidis, Leonidas Yulikov, Maxim Allain, Frédéric H.-T. Jeschke, Gunnar |
author_facet | Ritsch, Irina Esteban-Hofer, Laura Lehmann, Elisabeth Emmanouilidis, Leonidas Yulikov, Maxim Allain, Frédéric H.-T. Jeschke, Gunnar |
author_sort | Ritsch, Irina |
collection | PubMed |
description | Function of intrinsically disordered proteins may depend on deviation of their conformational ensemble from that of a random coil. Such deviation may be hard to characterize and quantify, if it is weak. We explored the potential of distance distributions between spin labels, as they can be measured by electron paramagnetic resonance techniques, for aiding such characterization. On the example of the intrinsically disordered N-terminal domain 1–267 of fused in sarcoma (FUS) we examined what such distance distributions can and cannot reveal on the random-coil reference state. On the example of the glycine-rich domain 188–320 of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) we studied whether deviation from a random-coil ensemble can be robustly detected with 19 distance distribution restraints. We discuss limitations imposed by ill-posedness of the conversion of primary data to distance distributions and propose overlap of distance distributions as a fit criterion that can tackle this problem. For testing consistency and size sufficiency of the restraint set, we propose jack-knife resampling. At current desktop computers, our approach is expected to be viable for domains up to 150 residues and for between 10 and 50 distance distribution restraints. |
format | Online Article Text |
id | pubmed-8072059 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80720592021-04-27 Characterization of Weak Protein Domain Structure by Spin-Label Distance Distributions Ritsch, Irina Esteban-Hofer, Laura Lehmann, Elisabeth Emmanouilidis, Leonidas Yulikov, Maxim Allain, Frédéric H.-T. Jeschke, Gunnar Front Mol Biosci Molecular Biosciences Function of intrinsically disordered proteins may depend on deviation of their conformational ensemble from that of a random coil. Such deviation may be hard to characterize and quantify, if it is weak. We explored the potential of distance distributions between spin labels, as they can be measured by electron paramagnetic resonance techniques, for aiding such characterization. On the example of the intrinsically disordered N-terminal domain 1–267 of fused in sarcoma (FUS) we examined what such distance distributions can and cannot reveal on the random-coil reference state. On the example of the glycine-rich domain 188–320 of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) we studied whether deviation from a random-coil ensemble can be robustly detected with 19 distance distribution restraints. We discuss limitations imposed by ill-posedness of the conversion of primary data to distance distributions and propose overlap of distance distributions as a fit criterion that can tackle this problem. For testing consistency and size sufficiency of the restraint set, we propose jack-knife resampling. At current desktop computers, our approach is expected to be viable for domains up to 150 residues and for between 10 and 50 distance distribution restraints. Frontiers Media S.A. 2021-04-12 /pmc/articles/PMC8072059/ /pubmed/33912586 http://dx.doi.org/10.3389/fmolb.2021.636599 Text en Copyright © 2021 Ritsch, Esteban-Hofer, Lehmann, Emmanouilidis, Yulikov, Allain and Jeschke. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Ritsch, Irina Esteban-Hofer, Laura Lehmann, Elisabeth Emmanouilidis, Leonidas Yulikov, Maxim Allain, Frédéric H.-T. Jeschke, Gunnar Characterization of Weak Protein Domain Structure by Spin-Label Distance Distributions |
title | Characterization of Weak Protein Domain Structure by Spin-Label Distance Distributions |
title_full | Characterization of Weak Protein Domain Structure by Spin-Label Distance Distributions |
title_fullStr | Characterization of Weak Protein Domain Structure by Spin-Label Distance Distributions |
title_full_unstemmed | Characterization of Weak Protein Domain Structure by Spin-Label Distance Distributions |
title_short | Characterization of Weak Protein Domain Structure by Spin-Label Distance Distributions |
title_sort | characterization of weak protein domain structure by spin-label distance distributions |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072059/ https://www.ncbi.nlm.nih.gov/pubmed/33912586 http://dx.doi.org/10.3389/fmolb.2021.636599 |
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