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Medical contrast agents as promising tools for biomacromolecular SAXS experiments
Small-angle X-ray scattering (SAXS) has become an indispensable tool in structural biology, complementing atomic-resolution techniques. It is sensitive to the electron-density difference between solubilized biomacromolecules and the buffer, and provides information on molecular masses, particle dime...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9435597/ https://www.ncbi.nlm.nih.gov/pubmed/36048152 http://dx.doi.org/10.1107/S2059798322007392 |
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author | Gabel, Frank Engilberge, Sylvain Schmitt, Emmanuelle Thureau, Aurélien Mechulam, Yves Pérez, Javier Girard, Eric |
author_facet | Gabel, Frank Engilberge, Sylvain Schmitt, Emmanuelle Thureau, Aurélien Mechulam, Yves Pérez, Javier Girard, Eric |
author_sort | Gabel, Frank |
collection | PubMed |
description | Small-angle X-ray scattering (SAXS) has become an indispensable tool in structural biology, complementing atomic-resolution techniques. It is sensitive to the electron-density difference between solubilized biomacromolecules and the buffer, and provides information on molecular masses, particle dimensions and interactions, low-resolution conformations and pair distance-distribution functions. When SAXS data are recorded at multiple contrasts, i.e. at different solvent electron densities, it is possible to probe, in addition to their overall shape, the internal electron-density profile of biomacromolecular assemblies. Unfortunately, contrast-variation SAXS has been limited by the range of solvent electron densities attainable using conventional co-solutes (for example sugars, glycerol and salt) and by the fact that some biological systems are destabilized in their presence. Here, SAXS contrast data from an oligomeric protein and a protein–RNA complex are presented in the presence of iohexol and Gd-HPDO3A, two electron-rich molecules that are used in biomedical imaging and that belong to the families of iodinated and lanthanide-based complexes, respectively. Moderate concentrations of both molecules allowed solvent electron densities matching those of proteins to be attained. While iohexol yielded higher solvent electron densities (per mole), it interacted specifically with the oligomeric protein and precipitated the protein–RNA complex. Gd-HPDO3A, while less efficient (per mole), did not disrupt the structural integrity of either system, and atomic models could be compared with the SAXS data. Due to their elevated solubility and electron density, their chemical inertness, as well as the possibility of altering their physico-chemical properties, lanthanide-based complexes represent a class of molecules with promising potential for contrast-variation SAXS experiments on diverse biomacromolecular systems. |
format | Online Article Text |
id | pubmed-9435597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-94355972022-09-19 Medical contrast agents as promising tools for biomacromolecular SAXS experiments Gabel, Frank Engilberge, Sylvain Schmitt, Emmanuelle Thureau, Aurélien Mechulam, Yves Pérez, Javier Girard, Eric Acta Crystallogr D Struct Biol Research Papers Small-angle X-ray scattering (SAXS) has become an indispensable tool in structural biology, complementing atomic-resolution techniques. It is sensitive to the electron-density difference between solubilized biomacromolecules and the buffer, and provides information on molecular masses, particle dimensions and interactions, low-resolution conformations and pair distance-distribution functions. When SAXS data are recorded at multiple contrasts, i.e. at different solvent electron densities, it is possible to probe, in addition to their overall shape, the internal electron-density profile of biomacromolecular assemblies. Unfortunately, contrast-variation SAXS has been limited by the range of solvent electron densities attainable using conventional co-solutes (for example sugars, glycerol and salt) and by the fact that some biological systems are destabilized in their presence. Here, SAXS contrast data from an oligomeric protein and a protein–RNA complex are presented in the presence of iohexol and Gd-HPDO3A, two electron-rich molecules that are used in biomedical imaging and that belong to the families of iodinated and lanthanide-based complexes, respectively. Moderate concentrations of both molecules allowed solvent electron densities matching those of proteins to be attained. While iohexol yielded higher solvent electron densities (per mole), it interacted specifically with the oligomeric protein and precipitated the protein–RNA complex. Gd-HPDO3A, while less efficient (per mole), did not disrupt the structural integrity of either system, and atomic models could be compared with the SAXS data. Due to their elevated solubility and electron density, their chemical inertness, as well as the possibility of altering their physico-chemical properties, lanthanide-based complexes represent a class of molecules with promising potential for contrast-variation SAXS experiments on diverse biomacromolecular systems. International Union of Crystallography 2022-08-09 /pmc/articles/PMC9435597/ /pubmed/36048152 http://dx.doi.org/10.1107/S2059798322007392 Text en © Frank Gabel et al. 2022 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited. |
spellingShingle | Research Papers Gabel, Frank Engilberge, Sylvain Schmitt, Emmanuelle Thureau, Aurélien Mechulam, Yves Pérez, Javier Girard, Eric Medical contrast agents as promising tools for biomacromolecular SAXS experiments |
title | Medical contrast agents as promising tools for biomacromolecular SAXS experiments |
title_full | Medical contrast agents as promising tools for biomacromolecular SAXS experiments |
title_fullStr | Medical contrast agents as promising tools for biomacromolecular SAXS experiments |
title_full_unstemmed | Medical contrast agents as promising tools for biomacromolecular SAXS experiments |
title_short | Medical contrast agents as promising tools for biomacromolecular SAXS experiments |
title_sort | medical contrast agents as promising tools for biomacromolecular saxs experiments |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9435597/ https://www.ncbi.nlm.nih.gov/pubmed/36048152 http://dx.doi.org/10.1107/S2059798322007392 |
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