Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein
- Autores
- Sacerdoti, Mariana; Gross, Lissy Zoe Florens; Riley, Andrew M.; Zehnder, Karin; Ghode, Abhijeet; Klinke, Sebastian; Anand, Ganesh Srinivasan; Paris, Kristina; Winkel, Angelika; Herbrand, Amanda K.; Godage, H. Yasmin; Cozier, Gyles E.; Süß, Evelyn; Schulze, Jörg O.; Pastor Flores, Daniel; Bollini, Mariela; Cappellari, María Victoria; Svergun, Dmitri; Gräwert, Melissa A.; Aramendia, Pedro Francisco; Leroux, Alejandro Ezequiel; Potter, Barry V. L.; Camacho, Carlos J.; Biondi, Ricardo Miguel
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The activation of at least 23 different mammalian kinases requires the phosphorylation of their hydrophobic motifs by the kinase PDK1. A linker connects the phosphoinositide-binding PH domain to the catalytic domain, which containsa docking site for substrates called the PIF pocket. Here, we used a chemical biologyapproach to show that PDK1 existed in equilibrium between at least three distinct conformations with differing substrate specificities.The inositol polyphosphate derivative HYG8 bound to the PH domain and disrupted PDK1 dimerization by stabilizing a monomeric conformation in which the PH domain associated with the catalytic domain and the PIF pocket wasaccessible. In the absence of lipids, HYG8 potently inhibited the phosphorylation of Akt (also termed PKB) but did not affect the intrinsic activity of PDK1 or the phosphorylation of SGK, which requires docking to the PIF pocket. In contrast, the small-molecule valsartan bound to the PIF pocket and stabilized a second distinct monomeric conformation. Our study reveals dynamic conformations of full-length PDK1 in which the location of the linker and the PH domain relative to the catalytic domain determines the selective phosphorylation of PDK1 substrates.The study further suggests new approaches for the design of drugs to selectively modulate signaling downstream of PDK1.
Fil: Sacerdoti, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Gross, Lissy Zoe Florens. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Riley, Andrew M.. University of Oxford; Reino Unido
Fil: Zehnder, Karin. Uuniversitat sklinikum Frankfurt; Alemania
Fil: Ghode, Abhijeet. Nanyang Technological University. Singapore Centre for Environmental Life Sciences Engineering; Singapur
Fil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Anand, Ganesh Srinivasan. National University Of Singapore; Singapur. Nanyang Technological University. Singapore Centre for Environmental Life Sciences Engineering; Singapur. State University of Pennsylvania; Estados Unidos
Fil: Paris, Kristina. University of Pittsburgh; Estados Unidos
Fil: Winkel, Angelika. Uuniversitat sklinikum Frankfurt; Alemania
Fil: Herbrand, Amanda K.. Uuniversitat sklinikum Frankfurt; Alemania
Fil: Godage, H. Yasmin. University of Bath; Reino Unido
Fil: Cozier, Gyles E.. University of Bath; Reino Unido
Fil: Süß, Evelyn. Uuniversitatsklinikum Frankfurt; Alemania
Fil: Schulze, Jörg O.. Uuniversitatsklinikum Frankfurt; Alemania
Fil: Pastor Flores, Daniel. Uuniversitatsklinikum Frankfurt; Alemania
Fil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina
Fil: Cappellari, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina
Fil: Svergun, Dmitri. European Molecular Biology Laboratory; Alemania
Fil: Gräwert, Melissa A.. European Molecular Biology Laboratory; Alemania
Fil: Aramendia, Pedro Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina
Fil: Leroux, Alejandro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Potter, Barry V. L.. University of Oxford; Reino Unido
Fil: Camacho, Carlos J.. University of Pittsburgh; Estados Unidos
Fil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina - Materia
- allostery
- Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/265321
Ver los metadatos del registro completo
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Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length proteinSacerdoti, MarianaGross, Lissy Zoe FlorensRiley, Andrew M.Zehnder, KarinGhode, AbhijeetKlinke, SebastianAnand, Ganesh SrinivasanParis, KristinaWinkel, AngelikaHerbrand, Amanda K.Godage, H. YasminCozier, Gyles E.Süß, EvelynSchulze, Jörg O.Pastor Flores, DanielBollini, MarielaCappellari, María VictoriaSvergun, DmitriGräwert, Melissa A.Aramendia, Pedro FranciscoLeroux, Alejandro EzequielPotter, Barry V. L.Camacho, Carlos J.Biondi, Ricardo Miguelallosteryhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The activation of at least 23 different mammalian kinases requires the phosphorylation of their hydrophobic motifs by the kinase PDK1. A linker connects the phosphoinositide-binding PH domain to the catalytic domain, which containsa docking site for substrates called the PIF pocket. Here, we used a chemical biologyapproach to show that PDK1 existed in equilibrium between at least three distinct conformations with differing substrate specificities.The inositol polyphosphate derivative HYG8 bound to the PH domain and disrupted PDK1 dimerization by stabilizing a monomeric conformation in which the PH domain associated with the catalytic domain and the PIF pocket wasaccessible. In the absence of lipids, HYG8 potently inhibited the phosphorylation of Akt (also termed PKB) but did not affect the intrinsic activity of PDK1 or the phosphorylation of SGK, which requires docking to the PIF pocket. In contrast, the small-molecule valsartan bound to the PIF pocket and stabilized a second distinct monomeric conformation. Our study reveals dynamic conformations of full-length PDK1 in which the location of the linker and the PH domain relative to the catalytic domain determines the selective phosphorylation of PDK1 substrates.The study further suggests new approaches for the design of drugs to selectively modulate signaling downstream of PDK1.Fil: Sacerdoti, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Gross, Lissy Zoe Florens. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Riley, Andrew M.. University of Oxford; Reino UnidoFil: Zehnder, Karin. Uuniversitat sklinikum Frankfurt; AlemaniaFil: Ghode, Abhijeet. Nanyang Technological University. Singapore Centre for Environmental Life Sciences Engineering; SingapurFil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Anand, Ganesh Srinivasan. National University Of Singapore; Singapur. Nanyang Technological University. Singapore Centre for Environmental Life Sciences Engineering; Singapur. State University of Pennsylvania; Estados UnidosFil: Paris, Kristina. University of Pittsburgh; Estados UnidosFil: Winkel, Angelika. Uuniversitat sklinikum Frankfurt; AlemaniaFil: Herbrand, Amanda K.. Uuniversitat sklinikum Frankfurt; AlemaniaFil: Godage, H. Yasmin. University of Bath; Reino UnidoFil: Cozier, Gyles E.. University of Bath; Reino UnidoFil: Süß, Evelyn. Uuniversitatsklinikum Frankfurt; AlemaniaFil: Schulze, Jörg O.. Uuniversitatsklinikum Frankfurt; AlemaniaFil: Pastor Flores, Daniel. Uuniversitatsklinikum Frankfurt; AlemaniaFil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Cappellari, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Svergun, Dmitri. European Molecular Biology Laboratory; AlemaniaFil: Gräwert, Melissa A.. European Molecular Biology Laboratory; AlemaniaFil: Aramendia, Pedro Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Leroux, Alejandro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Potter, Barry V. L.. University of Oxford; Reino UnidoFil: Camacho, Carlos J.. University of Pittsburgh; Estados UnidosFil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaAmerican Association for the Advancement of Science2023-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/265321Sacerdoti, Mariana; Gross, Lissy Zoe Florens; Riley, Andrew M.; Zehnder, Karin; Ghode, Abhijeet; et al.; Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein; American Association for the Advancement of Science; Science Signaling; 16; 789; 6-2023; 1-221945-08771937-9145CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/scisignal.add3184info:eu-repo/semantics/altIdentifier/doi/10.1126/scisignal.add3184info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:24Zoai:ri.conicet.gov.ar:11336/265321instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:52:24.799CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein |
| title |
Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein |
| spellingShingle |
Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein Sacerdoti, Mariana allostery |
| title_short |
Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein |
| title_full |
Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein |
| title_fullStr |
Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein |
| title_full_unstemmed |
Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein |
| title_sort |
Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein |
| dc.creator.none.fl_str_mv |
Sacerdoti, Mariana Gross, Lissy Zoe Florens Riley, Andrew M. Zehnder, Karin Ghode, Abhijeet Klinke, Sebastian Anand, Ganesh Srinivasan Paris, Kristina Winkel, Angelika Herbrand, Amanda K. Godage, H. Yasmin Cozier, Gyles E. Süß, Evelyn Schulze, Jörg O. Pastor Flores, Daniel Bollini, Mariela Cappellari, María Victoria Svergun, Dmitri Gräwert, Melissa A. Aramendia, Pedro Francisco Leroux, Alejandro Ezequiel Potter, Barry V. L. Camacho, Carlos J. Biondi, Ricardo Miguel |
| author |
Sacerdoti, Mariana |
| author_facet |
Sacerdoti, Mariana Gross, Lissy Zoe Florens Riley, Andrew M. Zehnder, Karin Ghode, Abhijeet Klinke, Sebastian Anand, Ganesh Srinivasan Paris, Kristina Winkel, Angelika Herbrand, Amanda K. Godage, H. Yasmin Cozier, Gyles E. Süß, Evelyn Schulze, Jörg O. Pastor Flores, Daniel Bollini, Mariela Cappellari, María Victoria Svergun, Dmitri Gräwert, Melissa A. Aramendia, Pedro Francisco Leroux, Alejandro Ezequiel Potter, Barry V. L. Camacho, Carlos J. Biondi, Ricardo Miguel |
| author_role |
author |
| author2 |
Gross, Lissy Zoe Florens Riley, Andrew M. Zehnder, Karin Ghode, Abhijeet Klinke, Sebastian Anand, Ganesh Srinivasan Paris, Kristina Winkel, Angelika Herbrand, Amanda K. Godage, H. Yasmin Cozier, Gyles E. Süß, Evelyn Schulze, Jörg O. Pastor Flores, Daniel Bollini, Mariela Cappellari, María Victoria Svergun, Dmitri Gräwert, Melissa A. Aramendia, Pedro Francisco Leroux, Alejandro Ezequiel Potter, Barry V. L. Camacho, Carlos J. Biondi, Ricardo Miguel |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
allostery |
| topic |
allostery |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
The activation of at least 23 different mammalian kinases requires the phosphorylation of their hydrophobic motifs by the kinase PDK1. A linker connects the phosphoinositide-binding PH domain to the catalytic domain, which containsa docking site for substrates called the PIF pocket. Here, we used a chemical biologyapproach to show that PDK1 existed in equilibrium between at least three distinct conformations with differing substrate specificities.The inositol polyphosphate derivative HYG8 bound to the PH domain and disrupted PDK1 dimerization by stabilizing a monomeric conformation in which the PH domain associated with the catalytic domain and the PIF pocket wasaccessible. In the absence of lipids, HYG8 potently inhibited the phosphorylation of Akt (also termed PKB) but did not affect the intrinsic activity of PDK1 or the phosphorylation of SGK, which requires docking to the PIF pocket. In contrast, the small-molecule valsartan bound to the PIF pocket and stabilized a second distinct monomeric conformation. Our study reveals dynamic conformations of full-length PDK1 in which the location of the linker and the PH domain relative to the catalytic domain determines the selective phosphorylation of PDK1 substrates.The study further suggests new approaches for the design of drugs to selectively modulate signaling downstream of PDK1. Fil: Sacerdoti, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Gross, Lissy Zoe Florens. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Riley, Andrew M.. University of Oxford; Reino Unido Fil: Zehnder, Karin. Uuniversitat sklinikum Frankfurt; Alemania Fil: Ghode, Abhijeet. Nanyang Technological University. Singapore Centre for Environmental Life Sciences Engineering; Singapur Fil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Anand, Ganesh Srinivasan. National University Of Singapore; Singapur. Nanyang Technological University. Singapore Centre for Environmental Life Sciences Engineering; Singapur. State University of Pennsylvania; Estados Unidos Fil: Paris, Kristina. University of Pittsburgh; Estados Unidos Fil: Winkel, Angelika. Uuniversitat sklinikum Frankfurt; Alemania Fil: Herbrand, Amanda K.. Uuniversitat sklinikum Frankfurt; Alemania Fil: Godage, H. Yasmin. University of Bath; Reino Unido Fil: Cozier, Gyles E.. University of Bath; Reino Unido Fil: Süß, Evelyn. Uuniversitatsklinikum Frankfurt; Alemania Fil: Schulze, Jörg O.. Uuniversitatsklinikum Frankfurt; Alemania Fil: Pastor Flores, Daniel. Uuniversitatsklinikum Frankfurt; Alemania Fil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina Fil: Cappellari, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina Fil: Svergun, Dmitri. European Molecular Biology Laboratory; Alemania Fil: Gräwert, Melissa A.. European Molecular Biology Laboratory; Alemania Fil: Aramendia, Pedro Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina Fil: Leroux, Alejandro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Potter, Barry V. L.. University of Oxford; Reino Unido Fil: Camacho, Carlos J.. University of Pittsburgh; Estados Unidos Fil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina |
| description |
The activation of at least 23 different mammalian kinases requires the phosphorylation of their hydrophobic motifs by the kinase PDK1. A linker connects the phosphoinositide-binding PH domain to the catalytic domain, which containsa docking site for substrates called the PIF pocket. Here, we used a chemical biologyapproach to show that PDK1 existed in equilibrium between at least three distinct conformations with differing substrate specificities.The inositol polyphosphate derivative HYG8 bound to the PH domain and disrupted PDK1 dimerization by stabilizing a monomeric conformation in which the PH domain associated with the catalytic domain and the PIF pocket wasaccessible. In the absence of lipids, HYG8 potently inhibited the phosphorylation of Akt (also termed PKB) but did not affect the intrinsic activity of PDK1 or the phosphorylation of SGK, which requires docking to the PIF pocket. In contrast, the small-molecule valsartan bound to the PIF pocket and stabilized a second distinct monomeric conformation. Our study reveals dynamic conformations of full-length PDK1 in which the location of the linker and the PH domain relative to the catalytic domain determines the selective phosphorylation of PDK1 substrates.The study further suggests new approaches for the design of drugs to selectively modulate signaling downstream of PDK1. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-06 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
| status_str |
publishedVersion |
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http://hdl.handle.net/11336/265321 Sacerdoti, Mariana; Gross, Lissy Zoe Florens; Riley, Andrew M.; Zehnder, Karin; Ghode, Abhijeet; et al.; Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein; American Association for the Advancement of Science; Science Signaling; 16; 789; 6-2023; 1-22 1945-0877 1937-9145 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/265321 |
| identifier_str_mv |
Sacerdoti, Mariana; Gross, Lissy Zoe Florens; Riley, Andrew M.; Zehnder, Karin; Ghode, Abhijeet; et al.; Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein; American Association for the Advancement of Science; Science Signaling; 16; 789; 6-2023; 1-22 1945-0877 1937-9145 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
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info:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/scisignal.add3184 info:eu-repo/semantics/altIdentifier/doi/10.1126/scisignal.add3184 |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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openAccess |
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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American Association for the Advancement of Science |
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American Association for the Advancement of Science |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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