The intrinsically disordered protein NUPR1 binds to phospholipids

The nuclear protein 1 (NUPR1) is an intrinsically disordered protein (IDP) involved in stress-mediated cellular conditions, with an interactome including many other partner proteins, as well as nucleic acids. We wondered whether its great conformational flexibility and biological versatility could i...

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Detalhes bibliográficos
Autores: Estaras, M, Rizzuti, B, Giudici, AM, Poveda, JA, Iovanna, JL, Santofimia-Castaño, P, Neira, JL
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2025
País:España
Recursos:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositório:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:dnet:r-fisabio___::974c6206196f75173c82dc5089031221
Acesso em linha:https://fisabio.portalinvestigacion.com/publicaciones/21013
Access Level:Acceso aberto
Palavra-chave:biolayer interferometry
intrinsically disordered protein
molecular docking
NMR
protein-lipid interactions
proximity ligation assay
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spelling The intrinsically disordered protein NUPR1 binds to phospholipidsEstaras, MRizzuti, BGiudici, AMPoveda, JAIovanna, JLSantofimia-Castaño, PNeira, JLbiolayer interferometryintrinsically disordered proteinmolecular dockingNMRprotein-lipid interactionsproximity ligation assayThe nuclear protein 1 (NUPR1) is an intrinsically disordered protein (IDP) involved in stress-mediated cellular conditions, with an interactome including many other partner proteins, as well as nucleic acids. We wondered whether its great conformational flexibility and biological versatility could include interactions with lipids. Binding between NUPR1 and phosphatidylserine (PS) and phosphatidylinositol biphosphate (PIP2) was verified in cellulo by using proximity ligation assay (PLA) techniques in MiaPaCa-2 cells. Binding in vitro was assayed against PS, and against PS in a mixture with phosphatidylcholine (PC), and it was confirmed by using nuclear magnetic resonance (NMR) and biolayer interferometry (BLI). Furthermore, results in silico also showed the association between NUPR1 and the lipids, occurring in a mostly aspecific way on the membrane surface, but with a slight preference for the binding through the protein hot-spot regions: the most common interaction sites with other molecular species: around Ala33 and Thr68. All together, these techniques unambiguously indicate that NUPR1 was bound to lipids. We discuss the potential biological consequences of our findings, including the possible relevance of NUPR1 in participating in the stability of membrane organelles, as well as in modulating cellular signaling.Wiley-Blackwell2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/21013Protein ScienceISSN: 1469896XISSNe: 09618368reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:dnet:r-fisabio___::974c6206196f75173c82dc50890312212026-06-11T12:45:17Z
dc.title.none.fl_str_mv The intrinsically disordered protein NUPR1 binds to phospholipids
title The intrinsically disordered protein NUPR1 binds to phospholipids
spellingShingle The intrinsically disordered protein NUPR1 binds to phospholipids
Estaras, M
biolayer interferometry
intrinsically disordered protein
molecular docking
NMR
protein-lipid interactions
proximity ligation assay
title_short The intrinsically disordered protein NUPR1 binds to phospholipids
title_full The intrinsically disordered protein NUPR1 binds to phospholipids
title_fullStr The intrinsically disordered protein NUPR1 binds to phospholipids
title_full_unstemmed The intrinsically disordered protein NUPR1 binds to phospholipids
title_sort The intrinsically disordered protein NUPR1 binds to phospholipids
dc.creator.none.fl_str_mv Estaras, M
Rizzuti, B
Giudici, AM
Poveda, JA
Iovanna, JL
Santofimia-Castaño, P
Neira, JL
author Estaras, M
author_facet Estaras, M
Rizzuti, B
Giudici, AM
Poveda, JA
Iovanna, JL
Santofimia-Castaño, P
Neira, JL
author_role author
author2 Rizzuti, B
Giudici, AM
Poveda, JA
Iovanna, JL
Santofimia-Castaño, P
Neira, JL
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv biolayer interferometry
intrinsically disordered protein
molecular docking
NMR
protein-lipid interactions
proximity ligation assay
topic biolayer interferometry
intrinsically disordered protein
molecular docking
NMR
protein-lipid interactions
proximity ligation assay
description The nuclear protein 1 (NUPR1) is an intrinsically disordered protein (IDP) involved in stress-mediated cellular conditions, with an interactome including many other partner proteins, as well as nucleic acids. We wondered whether its great conformational flexibility and biological versatility could include interactions with lipids. Binding between NUPR1 and phosphatidylserine (PS) and phosphatidylinositol biphosphate (PIP2) was verified in cellulo by using proximity ligation assay (PLA) techniques in MiaPaCa-2 cells. Binding in vitro was assayed against PS, and against PS in a mixture with phosphatidylcholine (PC), and it was confirmed by using nuclear magnetic resonance (NMR) and biolayer interferometry (BLI). Furthermore, results in silico also showed the association between NUPR1 and the lipids, occurring in a mostly aspecific way on the membrane surface, but with a slight preference for the binding through the protein hot-spot regions: the most common interaction sites with other molecular species: around Ala33 and Thr68. All together, these techniques unambiguously indicate that NUPR1 was bound to lipids. We discuss the potential biological consequences of our findings, including the possible relevance of NUPR1 in participating in the stability of membrane organelles, as well as in modulating cellular signaling.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/21013
url https://fisabio.portalinvestigacion.com/publicaciones/21013
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley-Blackwell
publisher.none.fl_str_mv Wiley-Blackwell
dc.source.none.fl_str_mv Protein Science
ISSN: 1469896X
ISSNe: 09618368
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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