Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein Antibodies

Autores
Acierno, Juan Pablo; Braden, Bradford C.; Klinke, Sebastian; Goldbaum, Fernando Alberto; Cauerff, Ana Albina
Año de publicación
2007
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The somatic mutations accumulated in variable and framework regions of antibodies produce structural changes that increase the affinity towards the antigen. This implies conformational and non covalent bonding changes at the paratope, as well as possible quaternary structure changes and rearrangements at the VH–VL interface. The consequences of the affinity maturation on the stability of the Fv domain were studied in a system composed of two closely related antibodies, F10.6.6 and D44.1, which recognize the same hen egg-white lysozyme (HEL) epitope. The mAb F10.6.6 has an affinity constant 700 times higher than D44.1, due to a higher surface complementarity to HEL. The structure of the free form of the Fab F10.6.6 presented here allows a comparative study of the conformational changes produced upon binding to antigen. By means of structural comparison, kinetics and thermodynamics of binding and stability studies on Fab and Fv fragments of both antibodies, we have determined that the affinity maturation process of anti-protein antibodies affects the shape of the combining site and the secondary structure content of the variable domain, stabilizes the VH–VL interaction, and consequently produces an increase of the Fv domain stability, improving the binding to antigen.
Fil: Acierno, Juan Pablo. 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: Braden, Bradford C.. Bowie State University; Estados Unidos
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: Goldbaum, Fernando Alberto. 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: Cauerff, Ana Albina. 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
Materia
Fv Domain
Affinity Maturation
Plasticity
Anti-Protein Antibodies
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:11336/31308
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/31308
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein AntibodiesAcierno, Juan PabloBraden, Bradford C.Klinke, SebastianGoldbaum, Fernando AlbertoCauerff, Ana AlbinaFv DomainAffinity MaturationPlasticityAnti-Protein Antibodieshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The somatic mutations accumulated in variable and framework regions of antibodies produce structural changes that increase the affinity towards the antigen. This implies conformational and non covalent bonding changes at the paratope, as well as possible quaternary structure changes and rearrangements at the VH–VL interface. The consequences of the affinity maturation on the stability of the Fv domain were studied in a system composed of two closely related antibodies, F10.6.6 and D44.1, which recognize the same hen egg-white lysozyme (HEL) epitope. The mAb F10.6.6 has an affinity constant 700 times higher than D44.1, due to a higher surface complementarity to HEL. The structure of the free form of the Fab F10.6.6 presented here allows a comparative study of the conformational changes produced upon binding to antigen. By means of structural comparison, kinetics and thermodynamics of binding and stability studies on Fab and Fv fragments of both antibodies, we have determined that the affinity maturation process of anti-protein antibodies affects the shape of the combining site and the secondary structure content of the variable domain, stabilizes the VH–VL interaction, and consequently produces an increase of the Fv domain stability, improving the binding to antigen.Fil: Acierno, Juan Pablo. 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: Braden, Bradford C.. Bowie State University; Estados UnidosFil: 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: Goldbaum, Fernando Alberto. 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: Cauerff, Ana Albina. 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; ArgentinaElsevier2007-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/31308Cauerff, Ana Albina; Goldbaum, Fernando Alberto; Klinke, Sebastian; Braden, Bradford C.; Acierno, Juan Pablo; Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein Antibodies; Elsevier; Journal Of Molecular Biology; 374; 1; 9-2007; 130-1460022-2836CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jmb.2007.09.005info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0022283607011692info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:36:16Zoai:ri.conicet.gov.ar:11336/31308instacron: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 15:36:16.975CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein Antibodies
title Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein Antibodies
spellingShingle Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein Antibodies
Acierno, Juan Pablo
Fv Domain
Affinity Maturation
Plasticity
Anti-Protein Antibodies
title_short Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein Antibodies
title_full Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein Antibodies
title_fullStr Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein Antibodies
title_full_unstemmed Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein Antibodies
title_sort Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein Antibodies
dc.creator.none.fl_str_mv Acierno, Juan Pablo
Braden, Bradford C.
Klinke, Sebastian
Goldbaum, Fernando Alberto
Cauerff, Ana Albina
author Acierno, Juan Pablo
author_facet Acierno, Juan Pablo
Braden, Bradford C.
Klinke, Sebastian
Goldbaum, Fernando Alberto
Cauerff, Ana Albina
author_role author
author2 Braden, Bradford C.
Klinke, Sebastian
Goldbaum, Fernando Alberto
Cauerff, Ana Albina
author2_role author
author
author
author
dc.subject.none.fl_str_mv Fv Domain
Affinity Maturation
Plasticity
Anti-Protein Antibodies
topic Fv Domain
Affinity Maturation
Plasticity
Anti-Protein Antibodies
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The somatic mutations accumulated in variable and framework regions of antibodies produce structural changes that increase the affinity towards the antigen. This implies conformational and non covalent bonding changes at the paratope, as well as possible quaternary structure changes and rearrangements at the VH–VL interface. The consequences of the affinity maturation on the stability of the Fv domain were studied in a system composed of two closely related antibodies, F10.6.6 and D44.1, which recognize the same hen egg-white lysozyme (HEL) epitope. The mAb F10.6.6 has an affinity constant 700 times higher than D44.1, due to a higher surface complementarity to HEL. The structure of the free form of the Fab F10.6.6 presented here allows a comparative study of the conformational changes produced upon binding to antigen. By means of structural comparison, kinetics and thermodynamics of binding and stability studies on Fab and Fv fragments of both antibodies, we have determined that the affinity maturation process of anti-protein antibodies affects the shape of the combining site and the secondary structure content of the variable domain, stabilizes the VH–VL interaction, and consequently produces an increase of the Fv domain stability, improving the binding to antigen.
Fil: Acierno, Juan Pablo. 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: Braden, Bradford C.. Bowie State University; Estados Unidos
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: Goldbaum, Fernando Alberto. 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: Cauerff, Ana Albina. 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
description The somatic mutations accumulated in variable and framework regions of antibodies produce structural changes that increase the affinity towards the antigen. This implies conformational and non covalent bonding changes at the paratope, as well as possible quaternary structure changes and rearrangements at the VH–VL interface. The consequences of the affinity maturation on the stability of the Fv domain were studied in a system composed of two closely related antibodies, F10.6.6 and D44.1, which recognize the same hen egg-white lysozyme (HEL) epitope. The mAb F10.6.6 has an affinity constant 700 times higher than D44.1, due to a higher surface complementarity to HEL. The structure of the free form of the Fab F10.6.6 presented here allows a comparative study of the conformational changes produced upon binding to antigen. By means of structural comparison, kinetics and thermodynamics of binding and stability studies on Fab and Fv fragments of both antibodies, we have determined that the affinity maturation process of anti-protein antibodies affects the shape of the combining site and the secondary structure content of the variable domain, stabilizes the VH–VL interaction, and consequently produces an increase of the Fv domain stability, improving the binding to antigen.
publishDate 2007
dc.date.none.fl_str_mv 2007-09
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/11336/31308
Cauerff, Ana Albina; Goldbaum, Fernando Alberto; Klinke, Sebastian; Braden, Bradford C.; Acierno, Juan Pablo; Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein Antibodies; Elsevier; Journal Of Molecular Biology; 374; 1; 9-2007; 130-146
0022-2836
CONICET Digital
CONICET
url http://hdl.handle.net/11336/31308
identifier_str_mv Cauerff, Ana Albina; Goldbaum, Fernando Alberto; Klinke, Sebastian; Braden, Bradford C.; Acierno, Juan Pablo; Affinity Maturation Increases the Stability and Plasticity of the Fv Domain of Anti-protein Antibodies; Elsevier; Journal Of Molecular Biology; 374; 1; 9-2007; 130-146
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.2007.09.005
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0022283607011692
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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 13.22299

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