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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...

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Autores principales: Kumra Ahnlide, Vibha, Kumra Ahnlide, Johannes, Wrighton, Sebastian, Beech, Jason P, Nordenfelt, Pontus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
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.
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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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