Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods

FGF-1 is a potent mitogen that, by interacting simultaneously with Heparan Sulfate Glycosaminoglycan HSGAG and the extracellular domains of its membrane receptor (FGFR), generates an intracellular signal that finally leads to cell division. The overall structure of the ternary complex Heparin:FGF-1:...

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Autores: García-Jiménez, María José, Gil-Caballero, Sergio, Canales Mayordomo, María Ángeles, Jiménez-Barbero, Jesús, de Paz, José L., Nieto, Pedro M.
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/19188
Acceso en línea:https://hdl.handle.net/20.500.14352/19188
Access Level:acceso abierto
Palabra clave:NMR
FGF-1
STD-NMR
transient complexes
Química orgánica (Química)
2306 Química Orgánica
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spelling Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR MethodsGarcía-Jiménez, María JoséGil-Caballero, SergioCanales Mayordomo, María ÁngelesJiménez-Barbero, Jesúsde Paz, José L.Nieto, Pedro M.NMRFGF-1STD-NMRtransient complexesQuímica orgánica (Química)2306 Química OrgánicaFGF-1 is a potent mitogen that, by interacting simultaneously with Heparan Sulfate Glycosaminoglycan HSGAG and the extracellular domains of its membrane receptor (FGFR), generates an intracellular signal that finally leads to cell division. The overall structure of the ternary complex Heparin:FGF-1:FGFR has been finally elucidated after some controversy and the interactions within the ternary complex have been deeply described. However, since the structure of the ternary complex was described, not much attention has been given to the molecular basis of the interaction between FGF-1 and the HSGAG. It is known that within the complex, the carbohydrate maintains the same helical structure of free heparin that leads to sulfate groups directed towards opposite directions along the molecular axis. The precise role of single individual interactions remains unclear, as sliding and/or rotating of the saccharide along the binding pocket are possibilities difficult to discard. The HSGAG binding pocket can be subdivided into two regions, the main one can accommodate a trisaccharide, while the other binds a disaccharide. We have studied and analyzed the interaction between FGF-1 and a library of trisaccharides by STD-NMR and selective longitudinal relaxation rates. The library of trisaccharides corresponds to the heparin backbone and it has been designed to interact with the main subsite of the protein.MDPIUniversidad Complutense de Madrid20172017-06-1720172017-06-17journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/19188reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/191882026-06-02T12:44:21Z
dc.title.none.fl_str_mv Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods
title Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods
spellingShingle Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods
García-Jiménez, María José
NMR
FGF-1
STD-NMR
transient complexes
Química orgánica (Química)
2306 Química Orgánica
title_short Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods
title_full Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods
title_fullStr Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods
title_full_unstemmed Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods
title_sort Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods
dc.creator.none.fl_str_mv García-Jiménez, María José
Gil-Caballero, Sergio
Canales Mayordomo, María Ángeles
Jiménez-Barbero, Jesús
de Paz, José L.
Nieto, Pedro M.
author García-Jiménez, María José
author_facet García-Jiménez, María José
Gil-Caballero, Sergio
Canales Mayordomo, María Ángeles
Jiménez-Barbero, Jesús
de Paz, José L.
Nieto, Pedro M.
author_role author
author2 Gil-Caballero, Sergio
Canales Mayordomo, María Ángeles
Jiménez-Barbero, Jesús
de Paz, José L.
Nieto, Pedro M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv NMR
FGF-1
STD-NMR
transient complexes
Química orgánica (Química)
2306 Química Orgánica
topic NMR
FGF-1
STD-NMR
transient complexes
Química orgánica (Química)
2306 Química Orgánica
description FGF-1 is a potent mitogen that, by interacting simultaneously with Heparan Sulfate Glycosaminoglycan HSGAG and the extracellular domains of its membrane receptor (FGFR), generates an intracellular signal that finally leads to cell division. The overall structure of the ternary complex Heparin:FGF-1:FGFR has been finally elucidated after some controversy and the interactions within the ternary complex have been deeply described. However, since the structure of the ternary complex was described, not much attention has been given to the molecular basis of the interaction between FGF-1 and the HSGAG. It is known that within the complex, the carbohydrate maintains the same helical structure of free heparin that leads to sulfate groups directed towards opposite directions along the molecular axis. The precise role of single individual interactions remains unclear, as sliding and/or rotating of the saccharide along the binding pocket are possibilities difficult to discard. The HSGAG binding pocket can be subdivided into two regions, the main one can accommodate a trisaccharide, while the other binds a disaccharide. We have studied and analyzed the interaction between FGF-1 and a library of trisaccharides by STD-NMR and selective longitudinal relaxation rates. The library of trisaccharides corresponds to the heparin backbone and it has been designed to interact with the main subsite of the protein.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-06-17
2017
2017-06-17
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/19188
url https://hdl.handle.net/20.500.14352/19188
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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