Specific Recognition of a DNA Immunogen by its Elicited Antibody

Autores
Sanguineti, Santiago; Centeno Crowley, Juan M.; Lodeiro, Anibal; Cerutti, Maria Laura; Goldbaum, Fernando Alberto; Wilson, Ian A.; Stanfield, Robyn L.; de Prat Gay, Gonzalo
Año de publicación
2007
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
DNA recognition by antibodies is a key feature of autoimmune diseases, yet model systems with structural information are very limited. The monoclonal antibody ED-10 recognizes one of the strands of the DNA duplex used in the immunogenic complex. Modifications of the 5′ end decrease the binding affinity and short oligonucleotides retain high binding affinity. We determined crystal structures for the Fab bound to a 6-mer oligonucleotide containing the specific sequence that raised the antibody and compared it with the unliganded Fab. Only the first two bases from the 5′ end (dTdC) display electron density and we observe four key hydrogen bonds at the interface. The thymine ring is stacked between TrpH50 and TrpH95, and the cytosine ring is packed against TyrL32. Upon DNA binding, TyrH97 and TrpH95 rearrange to allow subnanomolar binding affinity, five orders of magnitude higher than other reported complexes, possibly because of having gone through affinity maturation. This structure represents the first bona fide antibody DNA immunogen complex described in atomic detail.
Fil: Sanguineti, Santiago. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Centeno Crowley, Juan M.. Fundación Instituto Leloir; Argentina
Fil: Lodeiro, Anibal. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cerutti, Maria Laura. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Goldbaum, Fernando Alberto. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wilson, Ian A.. The Scripps Research Institute; Estados Unidos
Fil: Stanfield, Robyn L.. The Scripps Research Institute; Estados Unidos
Fil: de Prat Gay, Gonzalo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Anti-Dna
Antibody
Autoimmune
Dna Binding
Structure
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:11336/37739
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/37739
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Specific Recognition of a DNA Immunogen by its Elicited AntibodySanguineti, SantiagoCenteno Crowley, Juan M.Lodeiro, AnibalCerutti, Maria LauraGoldbaum, Fernando AlbertoWilson, Ian A.Stanfield, Robyn L.de Prat Gay, GonzaloAnti-DnaAntibodyAutoimmuneDna BindingStructurehttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1DNA recognition by antibodies is a key feature of autoimmune diseases, yet model systems with structural information are very limited. The monoclonal antibody ED-10 recognizes one of the strands of the DNA duplex used in the immunogenic complex. Modifications of the 5′ end decrease the binding affinity and short oligonucleotides retain high binding affinity. We determined crystal structures for the Fab bound to a 6-mer oligonucleotide containing the specific sequence that raised the antibody and compared it with the unliganded Fab. Only the first two bases from the 5′ end (dTdC) display electron density and we observe four key hydrogen bonds at the interface. The thymine ring is stacked between TrpH50 and TrpH95, and the cytosine ring is packed against TyrL32. Upon DNA binding, TyrH97 and TrpH95 rearrange to allow subnanomolar binding affinity, five orders of magnitude higher than other reported complexes, possibly because of having gone through affinity maturation. This structure represents the first bona fide antibody DNA immunogen complex described in atomic detail.Fil: Sanguineti, Santiago. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Centeno Crowley, Juan M.. Fundación Instituto Leloir; ArgentinaFil: Lodeiro, Anibal. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cerutti, Maria Laura. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goldbaum, Fernando Alberto. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wilson, Ian A.. The Scripps Research Institute; Estados UnidosFil: Stanfield, Robyn L.. The Scripps Research Institute; Estados UnidosFil: de Prat Gay, Gonzalo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAcademic Press Ltd - Elsevier Science Ltd2007-06info: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/11336/37739Sanguineti, Santiago; Centeno Crowley, Juan M.; Lodeiro, Anibal; Cerutti, Maria Laura; Goldbaum, Fernando Alberto; et al.; Specific Recognition of a DNA Immunogen by its Elicited Antibody; Academic Press Ltd - Elsevier Science Ltd; Journal Of Molecular Biology; 370; 1; 6-2007; 183-1950022-2836CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jmb.2007.04.046info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022283607005384info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:46:36Zoai:ri.conicet.gov.ar:11336/37739instacron: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:34982025-10-15 15:46:37.293CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Specific Recognition of a DNA Immunogen by its Elicited Antibody
title Specific Recognition of a DNA Immunogen by its Elicited Antibody
spellingShingle Specific Recognition of a DNA Immunogen by its Elicited Antibody
Sanguineti, Santiago
Anti-Dna
Antibody
Autoimmune
Dna Binding
Structure
title_short Specific Recognition of a DNA Immunogen by its Elicited Antibody
title_full Specific Recognition of a DNA Immunogen by its Elicited Antibody
title_fullStr Specific Recognition of a DNA Immunogen by its Elicited Antibody
title_full_unstemmed Specific Recognition of a DNA Immunogen by its Elicited Antibody
title_sort Specific Recognition of a DNA Immunogen by its Elicited Antibody
dc.creator.none.fl_str_mv Sanguineti, Santiago
Centeno Crowley, Juan M.
Lodeiro, Anibal
Cerutti, Maria Laura
Goldbaum, Fernando Alberto
Wilson, Ian A.
Stanfield, Robyn L.
de Prat Gay, Gonzalo
author Sanguineti, Santiago
author_facet Sanguineti, Santiago
Centeno Crowley, Juan M.
Lodeiro, Anibal
Cerutti, Maria Laura
Goldbaum, Fernando Alberto
Wilson, Ian A.
Stanfield, Robyn L.
de Prat Gay, Gonzalo
author_role author
author2 Centeno Crowley, Juan M.
Lodeiro, Anibal
Cerutti, Maria Laura
Goldbaum, Fernando Alberto
Wilson, Ian A.
Stanfield, Robyn L.
de Prat Gay, Gonzalo
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Anti-Dna
Antibody
Autoimmune
Dna Binding
Structure
topic Anti-Dna
Antibody
Autoimmune
Dna Binding
Structure
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv DNA recognition by antibodies is a key feature of autoimmune diseases, yet model systems with structural information are very limited. The monoclonal antibody ED-10 recognizes one of the strands of the DNA duplex used in the immunogenic complex. Modifications of the 5′ end decrease the binding affinity and short oligonucleotides retain high binding affinity. We determined crystal structures for the Fab bound to a 6-mer oligonucleotide containing the specific sequence that raised the antibody and compared it with the unliganded Fab. Only the first two bases from the 5′ end (dTdC) display electron density and we observe four key hydrogen bonds at the interface. The thymine ring is stacked between TrpH50 and TrpH95, and the cytosine ring is packed against TyrL32. Upon DNA binding, TyrH97 and TrpH95 rearrange to allow subnanomolar binding affinity, five orders of magnitude higher than other reported complexes, possibly because of having gone through affinity maturation. This structure represents the first bona fide antibody DNA immunogen complex described in atomic detail.
Fil: Sanguineti, Santiago. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Centeno Crowley, Juan M.. Fundación Instituto Leloir; Argentina
Fil: Lodeiro, Anibal. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cerutti, Maria Laura. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Goldbaum, Fernando Alberto. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wilson, Ian A.. The Scripps Research Institute; Estados Unidos
Fil: Stanfield, Robyn L.. The Scripps Research Institute; Estados Unidos
Fil: de Prat Gay, Gonzalo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description DNA recognition by antibodies is a key feature of autoimmune diseases, yet model systems with structural information are very limited. The monoclonal antibody ED-10 recognizes one of the strands of the DNA duplex used in the immunogenic complex. Modifications of the 5′ end decrease the binding affinity and short oligonucleotides retain high binding affinity. We determined crystal structures for the Fab bound to a 6-mer oligonucleotide containing the specific sequence that raised the antibody and compared it with the unliganded Fab. Only the first two bases from the 5′ end (dTdC) display electron density and we observe four key hydrogen bonds at the interface. The thymine ring is stacked between TrpH50 and TrpH95, and the cytosine ring is packed against TyrL32. Upon DNA binding, TyrH97 and TrpH95 rearrange to allow subnanomolar binding affinity, five orders of magnitude higher than other reported complexes, possibly because of having gone through affinity maturation. This structure represents the first bona fide antibody DNA immunogen complex described in atomic detail.
publishDate 2007
dc.date.none.fl_str_mv 2007-06
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
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/37739
Sanguineti, Santiago; Centeno Crowley, Juan M.; Lodeiro, Anibal; Cerutti, Maria Laura; Goldbaum, Fernando Alberto; et al.; Specific Recognition of a DNA Immunogen by its Elicited Antibody; Academic Press Ltd - Elsevier Science Ltd; Journal Of Molecular Biology; 370; 1; 6-2007; 183-195
0022-2836
CONICET Digital
CONICET
url http://hdl.handle.net/11336/37739
identifier_str_mv Sanguineti, Santiago; Centeno Crowley, Juan M.; Lodeiro, Anibal; Cerutti, Maria Laura; Goldbaum, Fernando Alberto; et al.; Specific Recognition of a DNA Immunogen by its Elicited Antibody; Academic Press Ltd - Elsevier Science Ltd; Journal Of Molecular Biology; 370; 1; 6-2007; 183-195
0022-2836
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jmb.2007.04.046
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022283607005384
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 Academic Press Ltd - Elsevier Science Ltd
publisher.none.fl_str_mv Academic Press Ltd - Elsevier Science Ltd
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
_version_ 1846083562734878720
score 13.22299

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