Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens

Autores
Quintana, Jon I.; Massaro, Mora; Cagnoni, Alejandro; Nuñez Franco, Reyes; Delgado, Sandra; Jiménez Osés, Gonzalo; Mariño, Karina Valeria; Rabinovich, Gabriel Adrián; Jiménez Barbero, Jesús; Ardá, Ana
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The dimeric architecture of tandem-repeat type galectins, such as galectin-4 (Gal-4), modulates their biological activities, although the underlying molecular mechanisms have remained elusive. Emerging evidence show that tandem-repeat galectins play an important role in innate immunity by recognizing carbohydrate antigens present on the surface of certain pathogens, which very often mimic the structures of the human self-glycan antigens. Herein, we have analyzed the binding preferences of the C-domain of Gal-4 (Gal-4C) towards the ABH-carbohydrate histo-blood antigens with different core presentations and their recognition features have been rationalized by employing a combined experimental approach including NMR, solid-phase and hemagglutination assays and molecular modeling. The data show that Gal-4C prefers A- over B-antigens (twofold in affinity), contrary to the N-domain (Gal-4N), although both domains share the same preference for the type-6 presentations. The behavior of the full-length tandem-repeat form (Gal-4FL) has been additionally scrutinized. ITC and NMR data demonstrate that both domains within Gal-4FL bind to the histo-blood antigens independently of each other, with no communication between them. In this context, the heterodimeric architecture does not play any major role, apart from the complementary A and B-antigen binding preferences. However, upon binding to a bacterial lipopolysaccharide (LPS) containing a multivalent version of an H-antigen mimetic as O-antigen, the significance of the galectin architecture was revealed. Indeed, our data point to the linker peptide domain and the F-face of the C-domain as key elements that provide Gal-4 with the ability to cross link multivalent ligands, beyond the glycan binding capacity of the dimer.
Fil: Quintana, Jon I.. CIC bioGUNE; España
Fil: Massaro, Mora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Cagnoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Nuñez Franco, Reyes. CIC bioGUNE; España
Fil: Delgado, Sandra. CIC bioGUNE; España
Fil: Jiménez Osés, Gonzalo. CIC bioGUNE; España. Basque Foundation for Science; España
Fil: Mariño, Karina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Jiménez Barbero, Jesús. CIC bioGUNE; España. Basque Foundation for Science; España. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias; España. Universidad del País Vasco; España
Fil: Ardá, Ana. CIC bioGUNE; España. Basque Foundation for Science; España
Materia
GALECTIN-4
CARBOHYDRATE-BINDING PROTEIN
TANDEM REPEAT
LINKER REGION
BLOOD GROUP ANTIGENS
LIPOPOLYSACCARIDE (LPS)
MOLECULAR RECOGNITION
NMR
AGGREGATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/242711
Acceder
id CONICETDig_b59cbc6ebc96a03e501549bfc655a8af
oai_identifier_str oai:ri.conicet.gov.ar:11336/242711
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigensQuintana, Jon I.Massaro, MoraCagnoni, AlejandroNuñez Franco, ReyesDelgado, SandraJiménez Osés, GonzaloMariño, Karina ValeriaRabinovich, Gabriel AdriánJiménez Barbero, JesúsArdá, AnaGALECTIN-4CARBOHYDRATE-BINDING PROTEINTANDEM REPEATLINKER REGIONBLOOD GROUP ANTIGENSLIPOPOLYSACCARIDE (LPS)MOLECULAR RECOGNITIONNMRAGGREGATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The dimeric architecture of tandem-repeat type galectins, such as galectin-4 (Gal-4), modulates their biological activities, although the underlying molecular mechanisms have remained elusive. Emerging evidence show that tandem-repeat galectins play an important role in innate immunity by recognizing carbohydrate antigens present on the surface of certain pathogens, which very often mimic the structures of the human self-glycan antigens. Herein, we have analyzed the binding preferences of the C-domain of Gal-4 (Gal-4C) towards the ABH-carbohydrate histo-blood antigens with different core presentations and their recognition features have been rationalized by employing a combined experimental approach including NMR, solid-phase and hemagglutination assays and molecular modeling. The data show that Gal-4C prefers A- over B-antigens (twofold in affinity), contrary to the N-domain (Gal-4N), although both domains share the same preference for the type-6 presentations. The behavior of the full-length tandem-repeat form (Gal-4FL) has been additionally scrutinized. ITC and NMR data demonstrate that both domains within Gal-4FL bind to the histo-blood antigens independently of each other, with no communication between them. In this context, the heterodimeric architecture does not play any major role, apart from the complementary A and B-antigen binding preferences. However, upon binding to a bacterial lipopolysaccharide (LPS) containing a multivalent version of an H-antigen mimetic as O-antigen, the significance of the galectin architecture was revealed. Indeed, our data point to the linker peptide domain and the F-face of the C-domain as key elements that provide Gal-4 with the ability to cross link multivalent ligands, beyond the glycan binding capacity of the dimer.Fil: Quintana, Jon I.. CIC bioGUNE; EspañaFil: Massaro, Mora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Cagnoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Nuñez Franco, Reyes. CIC bioGUNE; EspañaFil: Delgado, Sandra. CIC bioGUNE; EspañaFil: Jiménez Osés, Gonzalo. CIC bioGUNE; España. Basque Foundation for Science; EspañaFil: Mariño, Karina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Jiménez Barbero, Jesús. CIC bioGUNE; España. Basque Foundation for Science; España. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias; España. Universidad del País Vasco; EspañaFil: Ardá, Ana. CIC bioGUNE; España. Basque Foundation for Science; EspañaAmerican Society for Biochemistry and Molecular Biology2024-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/242711Quintana, Jon I.; Massaro, Mora; Cagnoni, Alejandro; Nuñez Franco, Reyes; Delgado, Sandra; et al.; Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 300; 8; 8-2024; 1-160021-9258CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0021925824020787info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jbc.2024.107577info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-04-08T11:34:24Zoai:ri.conicet.gov.ar:11336/242711instacron: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:34982026-04-08 11:34:25.193CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens
title Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens
spellingShingle Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens
Quintana, Jon I.
GALECTIN-4
CARBOHYDRATE-BINDING PROTEIN
TANDEM REPEAT
LINKER REGION
BLOOD GROUP ANTIGENS
LIPOPOLYSACCARIDE (LPS)
MOLECULAR RECOGNITION
NMR
AGGREGATION
title_short Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens
title_full Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens
title_fullStr Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens
title_full_unstemmed Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens
title_sort Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens
dc.creator.none.fl_str_mv Quintana, Jon I.
Massaro, Mora
Cagnoni, Alejandro
Nuñez Franco, Reyes
Delgado, Sandra
Jiménez Osés, Gonzalo
Mariño, Karina Valeria
Rabinovich, Gabriel Adrián
Jiménez Barbero, Jesús
Ardá, Ana
author Quintana, Jon I.
author_facet Quintana, Jon I.
Massaro, Mora
Cagnoni, Alejandro
Nuñez Franco, Reyes
Delgado, Sandra
Jiménez Osés, Gonzalo
Mariño, Karina Valeria
Rabinovich, Gabriel Adrián
Jiménez Barbero, Jesús
Ardá, Ana
author_role author
author2 Massaro, Mora
Cagnoni, Alejandro
Nuñez Franco, Reyes
Delgado, Sandra
Jiménez Osés, Gonzalo
Mariño, Karina Valeria
Rabinovich, Gabriel Adrián
Jiménez Barbero, Jesús
Ardá, Ana
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GALECTIN-4
CARBOHYDRATE-BINDING PROTEIN
TANDEM REPEAT
LINKER REGION
BLOOD GROUP ANTIGENS
LIPOPOLYSACCARIDE (LPS)
MOLECULAR RECOGNITION
NMR
AGGREGATION
topic GALECTIN-4
CARBOHYDRATE-BINDING PROTEIN
TANDEM REPEAT
LINKER REGION
BLOOD GROUP ANTIGENS
LIPOPOLYSACCARIDE (LPS)
MOLECULAR RECOGNITION
NMR
AGGREGATION
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 dimeric architecture of tandem-repeat type galectins, such as galectin-4 (Gal-4), modulates their biological activities, although the underlying molecular mechanisms have remained elusive. Emerging evidence show that tandem-repeat galectins play an important role in innate immunity by recognizing carbohydrate antigens present on the surface of certain pathogens, which very often mimic the structures of the human self-glycan antigens. Herein, we have analyzed the binding preferences of the C-domain of Gal-4 (Gal-4C) towards the ABH-carbohydrate histo-blood antigens with different core presentations and their recognition features have been rationalized by employing a combined experimental approach including NMR, solid-phase and hemagglutination assays and molecular modeling. The data show that Gal-4C prefers A- over B-antigens (twofold in affinity), contrary to the N-domain (Gal-4N), although both domains share the same preference for the type-6 presentations. The behavior of the full-length tandem-repeat form (Gal-4FL) has been additionally scrutinized. ITC and NMR data demonstrate that both domains within Gal-4FL bind to the histo-blood antigens independently of each other, with no communication between them. In this context, the heterodimeric architecture does not play any major role, apart from the complementary A and B-antigen binding preferences. However, upon binding to a bacterial lipopolysaccharide (LPS) containing a multivalent version of an H-antigen mimetic as O-antigen, the significance of the galectin architecture was revealed. Indeed, our data point to the linker peptide domain and the F-face of the C-domain as key elements that provide Gal-4 with the ability to cross link multivalent ligands, beyond the glycan binding capacity of the dimer.
Fil: Quintana, Jon I.. CIC bioGUNE; España
Fil: Massaro, Mora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Cagnoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Nuñez Franco, Reyes. CIC bioGUNE; España
Fil: Delgado, Sandra. CIC bioGUNE; España
Fil: Jiménez Osés, Gonzalo. CIC bioGUNE; España. Basque Foundation for Science; España
Fil: Mariño, Karina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Jiménez Barbero, Jesús. CIC bioGUNE; España. Basque Foundation for Science; España. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias; España. Universidad del País Vasco; España
Fil: Ardá, Ana. CIC bioGUNE; España. Basque Foundation for Science; España
description The dimeric architecture of tandem-repeat type galectins, such as galectin-4 (Gal-4), modulates their biological activities, although the underlying molecular mechanisms have remained elusive. Emerging evidence show that tandem-repeat galectins play an important role in innate immunity by recognizing carbohydrate antigens present on the surface of certain pathogens, which very often mimic the structures of the human self-glycan antigens. Herein, we have analyzed the binding preferences of the C-domain of Gal-4 (Gal-4C) towards the ABH-carbohydrate histo-blood antigens with different core presentations and their recognition features have been rationalized by employing a combined experimental approach including NMR, solid-phase and hemagglutination assays and molecular modeling. The data show that Gal-4C prefers A- over B-antigens (twofold in affinity), contrary to the N-domain (Gal-4N), although both domains share the same preference for the type-6 presentations. The behavior of the full-length tandem-repeat form (Gal-4FL) has been additionally scrutinized. ITC and NMR data demonstrate that both domains within Gal-4FL bind to the histo-blood antigens independently of each other, with no communication between them. In this context, the heterodimeric architecture does not play any major role, apart from the complementary A and B-antigen binding preferences. However, upon binding to a bacterial lipopolysaccharide (LPS) containing a multivalent version of an H-antigen mimetic as O-antigen, the significance of the galectin architecture was revealed. Indeed, our data point to the linker peptide domain and the F-face of the C-domain as key elements that provide Gal-4 with the ability to cross link multivalent ligands, beyond the glycan binding capacity of the dimer.
publishDate 2024
dc.date.none.fl_str_mv 2024-08
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
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/242711
Quintana, Jon I.; Massaro, Mora; Cagnoni, Alejandro; Nuñez Franco, Reyes; Delgado, Sandra; et al.; Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 300; 8; 8-2024; 1-16
0021-9258
CONICET Digital
CONICET
url http://hdl.handle.net/11336/242711
identifier_str_mv Quintana, Jon I.; Massaro, Mora; Cagnoni, Alejandro; Nuñez Franco, Reyes; Delgado, Sandra; et al.; Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 300; 8; 8-2024; 1-16
0021-9258
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0021925824020787
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jbc.2024.107577
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.018236

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