Nanobodies as tools for studying human frataxin biology

20 pages, 10 figures, 1 table

Detalles Bibliográficos
Autores: Pignataro, María Florencia, Fernández, Natalia Brenda, Garay-Álvarez, Alba, Pavan, María Florencia, Molina, Rafael, Muñoz, Inés G., Grossi, Julián, Noguera, Martín, Vila, Antonella, García, Augusto E., Gentili, Hernán G., Rodríguez, Naira Antonia, Aran, Martín, Parreño, Viviana, Bok, Marina, Hermoso, Juan A., Ibañez, Lorena Itatí, Santos, Javier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::ebe143c806b58f6f48d87267beb91534
Acceso en línea:http://hdl.handle.net/10261/430105
https://api.elsevier.com/content/abstract/scopus_id/105029532306
Access Level:acceso abierto
Palabra clave:http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
biology
Life sciences
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dc.title.none.fl_str_mv Nanobodies as tools for studying human frataxin biology
title Nanobodies as tools for studying human frataxin biology
spellingShingle Nanobodies as tools for studying human frataxin biology
Pignataro, María Florencia
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
biology
Life sciences
title_short Nanobodies as tools for studying human frataxin biology
title_full Nanobodies as tools for studying human frataxin biology
title_fullStr Nanobodies as tools for studying human frataxin biology
title_full_unstemmed Nanobodies as tools for studying human frataxin biology
title_sort Nanobodies as tools for studying human frataxin biology
dc.creator.none.fl_str_mv Pignataro, María Florencia
Fernández, Natalia Brenda
Garay-Álvarez, Alba
Pavan, María Florencia
Molina, Rafael
Muñoz, Inés G.
Grossi, Julián
Noguera, Martín
Vila, Antonella
García, Augusto E.
Gentili, Hernán G.
Rodríguez, Naira Antonia
Aran, Martín
Parreño, Viviana
Bok, Marina
Hermoso, Juan A.
Ibañez, Lorena Itatí
Santos, Javier
author Pignataro, María Florencia
author_facet Pignataro, María Florencia
Fernández, Natalia Brenda
Garay-Álvarez, Alba
Pavan, María Florencia
Molina, Rafael
Muñoz, Inés G.
Grossi, Julián
Noguera, Martín
Vila, Antonella
García, Augusto E.
Gentili, Hernán G.
Rodríguez, Naira Antonia
Aran, Martín
Parreño, Viviana
Bok, Marina
Hermoso, Juan A.
Ibañez, Lorena Itatí
Santos, Javier
author_role author
author2 Fernández, Natalia Brenda
Garay-Álvarez, Alba
Pavan, María Florencia
Molina, Rafael
Muñoz, Inés G.
Grossi, Julián
Noguera, Martín
Vila, Antonella
García, Augusto E.
Gentili, Hernán G.
Rodríguez, Naira Antonia
Aran, Martín
Parreño, Viviana
Bok, Marina
Hermoso, Juan A.
Ibañez, Lorena Itatí
Santos, Javier
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad de Buenos Aires
Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina)
Friedreich´s Ataxia Research Alliance
Ministerio de Ciencia e Innovación (España)
ALBA Synchrotron
Pignataro, María Florencia [0000-0002-5398-8724]
#NODATA#
Garay-Álvarez, Alba [0009-0001-6544-7327]
Pavan, María Florencia [0009-0007-3646-5749]
Molina, Rafael [0000-0002-6443-4989]
Muñoz, Inés G. [0000-0001-6732-4059]
#NODATA#
Noguera, Martín [0000-0001-5868-3834]
#NODATA#
García, Augusto E. [0000-0001-7668-2050]
#NODATA#
#NODATA#
#NODATA#
#NODATA#
#NODATA#
Hermoso, Juan A. [0000-0002-1862-8950]
Ibañez, Lorena Itatí [0000-0002-9393-2004]
Santos, Javier [0000-0002-1140-8234]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
biology
Life sciences
topic http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
biology
Life sciences
description 20 pages, 10 figures, 1 table
publishDate 2026
dc.date.none.fl_str_mv 2026
2026
2026
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/430105
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url http://hdl.handle.net/10261/430105
https://api.elsevier.com/content/abstract/scopus_id/105029532306
dc.language.none.fl_str_mv Inglés
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-115331GB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-153118OB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-136750NB-I00
https://doi.org/10.1038/s42003-025-09458-x

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dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
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spelling Nanobodies as tools for studying human frataxin biologyPignataro, María FlorenciaFernández, Natalia BrendaGaray-Álvarez, AlbaPavan, María FlorenciaMolina, RafaelMuñoz, Inés G.Grossi, JuliánNoguera, MartínVila, AntonellaGarcía, Augusto E.Gentili, Hernán G.Rodríguez, Naira AntoniaAran, MartínParreño, VivianaBok, MarinaHermoso, Juan A.Ibañez, Lorena ItatíSantos, Javierhttp://metadata.un.org/sdg/3Ensure healthy lives and promote well-being for all at all agesbiologyLife sciences20 pages, 10 figures, 1 tableIron-sulfur clusters are essential cofactors for the accurate cellular function of many proteins. In eukaryotic cells, the biogenesis of most iron-sulfur clusters occurs in the mitochondria and involves the action of the Cys desulfurase supercomplex, which is activated by the protein frataxin (FXN). The decrease of FXN expression and/or function results in Friedreich's ataxia (FRDA).In this work, several nanobodies specific to human FXN were selected via phage display, demonstrating a wide range of effects on Cys desulfurase activity and a strong interaction with FXN. Nanobody interaction stabilized wild-type and FRDA-related FXN variants in vitro. FXN-nanobody complexes were characterized by NMR, SAXS, and X-ray crystallography. Additionally, Nanobody expression was studied in human cells. The subcellular localization, direct interaction with FXN by in situ proximity ligation assay, effect on cell viability, Fe-S-dependent enzymatic activities, and oxygen consumption rates were analyzed. Significantly, nanobody expression did not alter these key metabolic variables, suggesting that the interaction with FXN did not disrupt the pathway.As a whole, our results suggest that nanobodies can serve as binding partners for mitochondrial FXN. However, the specific effect of the nanobodies on the conformational stability of FRDA-related FXN variants in cells should be investigated.This work was supported by Universidad de Buenos Aires UBACyT20020190100338BA, CONICET, and Friedreich´s Ataxia Research Alliance (FARA, grant 2023-2025). The work in Spain was funded by the Spanish Ministry of Science and Innovation by grants PID2020-115331GB-100 and PID2023-153118OB-100 to J.A.H., and PID2022-136750NB-I00 to R.M. We gratefully acknowledge the staff of the XALOC beamline at the ALBA Synchrotron in Barcelona for their valuable assistance with data collection. We would also like to thank Lic. Alejo Cantoia, Dr. Gernán Rosano, and Dr. Eduardo Ceccarelli from the UEM-IBR (Mass spectrometry unit of the Instituto de Biología Molecular y Celular de Rosario, Argentina) for technical assistance and data processing of LC-MS experiments.Peer reviewedNature Publishing GroupUniversidad de Buenos AiresConsejo Nacional de Investigaciones Científicas y Técnicas (Argentina)Friedreich´s Ataxia Research AllianceMinisterio de Ciencia e Innovación (España)ALBA SynchrotronPignataro, María Florencia [0000-0002-5398-8724]#NODATA#Garay-Álvarez, Alba [0009-0001-6544-7327]Pavan, María Florencia [0009-0007-3646-5749]Molina, Rafael [0000-0002-6443-4989]Muñoz, Inés G. [0000-0001-6732-4059]#NODATA#Noguera, Martín [0000-0001-5868-3834]#NODATA#García, Augusto E. [0000-0001-7668-2050]#NODATA##NODATA##NODATA##NODATA##NODATA#Hermoso, Juan A. [0000-0002-1862-8950]Ibañez, Lorena Itatí [0000-0002-9393-2004]Santos, Javier [0000-0002-1140-8234]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262026info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/430105https://api.elsevier.com/content/abstract/scopus_id/105029532306reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-115331GB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-153118OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-136750NB-I00https://doi.org/10.1038/s42003-025-09458-xSíinfo:eu-repo/semantics/openAccessoai:dnet:digitalcsic_::ebe143c806b58f6f48d87267beb915342026-05-22T06:33:51Z
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