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Nanoscale binding site localization by molecular distance estimation on native cell surfaces using topological image averaging
Antibody binding to cell surface proteins plays a crucial role in immunity, and the location of an epitope can altogether determine the immunological outcome of a host-target interaction. Techniques available today for epitope identification are costly, time-consuming, and unsuited for high-throughp...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8871386/ https://www.ncbi.nlm.nih.gov/pubmed/35200140 http://dx.doi.org/10.7554/eLife.64709 |
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author | Kumra Ahnlide, Vibha Kumra Ahnlide, Johannes Wrighton, Sebastian Beech, Jason P Nordenfelt, Pontus |
author_facet | Kumra Ahnlide, Vibha Kumra Ahnlide, Johannes Wrighton, Sebastian Beech, Jason P Nordenfelt, Pontus |
author_sort | Kumra Ahnlide, Vibha |
collection | PubMed |
description | Antibody binding to cell surface proteins plays a crucial role in immunity, and the location of an epitope can altogether determine the immunological outcome of a host-target interaction. Techniques available today for epitope identification are costly, time-consuming, and unsuited for high-throughput analysis. Fast and efficient screening of epitope location can be useful for the development of therapeutic monoclonal antibodies and vaccines. Cellular morphology typically varies, and antibodies often bind heterogeneously across a cell surface, making traditional particle-averaging strategies challenging for accurate native antibody localization. In the present work, we have developed a method, SiteLoc, for imaging-based molecular localization on cellular surface proteins. Nanometer-scale resolution is achieved through localization in one dimension, namely, the distance from a bound ligand to a reference surface. This is done by using topological image averaging. Our results show that this method is well suited for antibody binding site measurements on native cell surface morphology and that it can be applied to other molecular distance estimations as well. |
format | Online Article Text |
id | pubmed-8871386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-88713862022-02-25 Nanoscale binding site localization by molecular distance estimation on native cell surfaces using topological image averaging Kumra Ahnlide, Vibha Kumra Ahnlide, Johannes Wrighton, Sebastian Beech, Jason P Nordenfelt, Pontus eLife Cell Biology Antibody binding to cell surface proteins plays a crucial role in immunity, and the location of an epitope can altogether determine the immunological outcome of a host-target interaction. Techniques available today for epitope identification are costly, time-consuming, and unsuited for high-throughput analysis. Fast and efficient screening of epitope location can be useful for the development of therapeutic monoclonal antibodies and vaccines. Cellular morphology typically varies, and antibodies often bind heterogeneously across a cell surface, making traditional particle-averaging strategies challenging for accurate native antibody localization. In the present work, we have developed a method, SiteLoc, for imaging-based molecular localization on cellular surface proteins. Nanometer-scale resolution is achieved through localization in one dimension, namely, the distance from a bound ligand to a reference surface. This is done by using topological image averaging. Our results show that this method is well suited for antibody binding site measurements on native cell surface morphology and that it can be applied to other molecular distance estimations as well. eLife Sciences Publications, Ltd 2022-02-24 /pmc/articles/PMC8871386/ /pubmed/35200140 http://dx.doi.org/10.7554/eLife.64709 Text en © 2022, Kumra Ahnlide et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Kumra Ahnlide, Vibha Kumra Ahnlide, Johannes Wrighton, Sebastian Beech, Jason P Nordenfelt, Pontus Nanoscale binding site localization by molecular distance estimation on native cell surfaces using topological image averaging |
title | Nanoscale binding site localization by molecular distance estimation on native cell surfaces using topological image averaging |
title_full | Nanoscale binding site localization by molecular distance estimation on native cell surfaces using topological image averaging |
title_fullStr | Nanoscale binding site localization by molecular distance estimation on native cell surfaces using topological image averaging |
title_full_unstemmed | Nanoscale binding site localization by molecular distance estimation on native cell surfaces using topological image averaging |
title_short | Nanoscale binding site localization by molecular distance estimation on native cell surfaces using topological image averaging |
title_sort | nanoscale binding site localization by molecular distance estimation on native cell surfaces using topological image averaging |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8871386/ https://www.ncbi.nlm.nih.gov/pubmed/35200140 http://dx.doi.org/10.7554/eLife.64709 |
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