Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding protein

Autores
Franchini, Gisela Raquel; Curto, Lucrecia María; Caramelo, Julio Javier; Delfino, Jose Maria
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A lingering issue in the area of protein engineering is the optimal design of beta motifs. In this regard, the framework provided by intestinal fatty acid binding protein (IFABP) was successfully chosen to explore the consequences on structure and function of the redesign of natural motifs. A truncated form of IFABP (Delta 98 Delta) served to illustrate the nonintuitive notion that the integrity of the beta-barrel can indeed be compromised with no effect on the ability to attain a native-like fold. This is most likely the outcome of the key role played by the preservation of essential core residues. In the search for the minimal structural determinants of this fold, Delta 98 Delta offered room for further intervention. A dissection of this protein leads to a new abridged variant, Delta 78 Delta, containing 60% of the amino acids of IFABP. Spectroscopic analyses indicate that Delta 78 Delta retains substantial beta-sheet content and preserves tertiary interactions, displaying cooperative unfolding and binding activity. Most strikingly, this construct adopts a remarkably stable dimeric structure in solution. This phenomenon takes advantage of the inherent structural plasticity of this motif, likely profitting from edge-to-edge interactions between beta-sheets, whereas avoiding the most commonly occurring outcome represented by aggregation.
Fil: Franchini, Gisela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Curto, Lucrecia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Caramelo, Julio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Delfino, Jose Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Materia
Fatty Acid Binding Proteins
Folding
Dimerization
Beta Barrel
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/25569
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding proteinFranchini, Gisela RaquelCurto, Lucrecia MaríaCaramelo, Julio JavierDelfino, Jose MariaFatty Acid Binding ProteinsFoldingDimerizationBeta Barrelhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1A lingering issue in the area of protein engineering is the optimal design of beta motifs. In this regard, the framework provided by intestinal fatty acid binding protein (IFABP) was successfully chosen to explore the consequences on structure and function of the redesign of natural motifs. A truncated form of IFABP (Delta 98 Delta) served to illustrate the nonintuitive notion that the integrity of the beta-barrel can indeed be compromised with no effect on the ability to attain a native-like fold. This is most likely the outcome of the key role played by the preservation of essential core residues. In the search for the minimal structural determinants of this fold, Delta 98 Delta offered room for further intervention. A dissection of this protein leads to a new abridged variant, Delta 78 Delta, containing 60% of the amino acids of IFABP. Spectroscopic analyses indicate that Delta 78 Delta retains substantial beta-sheet content and preserves tertiary interactions, displaying cooperative unfolding and binding activity. Most strikingly, this construct adopts a remarkably stable dimeric structure in solution. This phenomenon takes advantage of the inherent structural plasticity of this motif, likely profitting from edge-to-edge interactions between beta-sheets, whereas avoiding the most commonly occurring outcome represented by aggregation.Fil: Franchini, Gisela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Curto, Lucrecia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Caramelo, Julio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Delfino, Jose Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaWiley2009-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25569Franchini, Gisela Raquel; Curto, Lucrecia María; Caramelo, Julio Javier; Delfino, Jose Maria; Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding protein; Wiley; Protein Science; 18; 12; 12-2009; 2592-26020961-83681469-896XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/pro.273/abstractinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821277/info:eu-repo/semantics/altIdentifier/doi/10.1002/pro.273info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:05:40Zoai:ri.conicet.gov.ar:11336/25569instacron: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 10:05:40.876CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding protein
title Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding protein
spellingShingle Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding protein
Franchini, Gisela Raquel
Fatty Acid Binding Proteins
Folding
Dimerization
Beta Barrel
title_short Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding protein
title_full Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding protein
title_fullStr Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding protein
title_full_unstemmed Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding protein
title_sort Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding protein
dc.creator.none.fl_str_mv Franchini, Gisela Raquel
Curto, Lucrecia María
Caramelo, Julio Javier
Delfino, Jose Maria
author Franchini, Gisela Raquel
author_facet Franchini, Gisela Raquel
Curto, Lucrecia María
Caramelo, Julio Javier
Delfino, Jose Maria
author_role author
author2 Curto, Lucrecia María
Caramelo, Julio Javier
Delfino, Jose Maria
author2_role author
author
author
dc.subject.none.fl_str_mv Fatty Acid Binding Proteins
Folding
Dimerization
Beta Barrel
topic Fatty Acid Binding Proteins
Folding
Dimerization
Beta Barrel
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A lingering issue in the area of protein engineering is the optimal design of beta motifs. In this regard, the framework provided by intestinal fatty acid binding protein (IFABP) was successfully chosen to explore the consequences on structure and function of the redesign of natural motifs. A truncated form of IFABP (Delta 98 Delta) served to illustrate the nonintuitive notion that the integrity of the beta-barrel can indeed be compromised with no effect on the ability to attain a native-like fold. This is most likely the outcome of the key role played by the preservation of essential core residues. In the search for the minimal structural determinants of this fold, Delta 98 Delta offered room for further intervention. A dissection of this protein leads to a new abridged variant, Delta 78 Delta, containing 60% of the amino acids of IFABP. Spectroscopic analyses indicate that Delta 78 Delta retains substantial beta-sheet content and preserves tertiary interactions, displaying cooperative unfolding and binding activity. Most strikingly, this construct adopts a remarkably stable dimeric structure in solution. This phenomenon takes advantage of the inherent structural plasticity of this motif, likely profitting from edge-to-edge interactions between beta-sheets, whereas avoiding the most commonly occurring outcome represented by aggregation.
Fil: Franchini, Gisela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Curto, Lucrecia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Caramelo, Julio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Delfino, Jose Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
description A lingering issue in the area of protein engineering is the optimal design of beta motifs. In this regard, the framework provided by intestinal fatty acid binding protein (IFABP) was successfully chosen to explore the consequences on structure and function of the redesign of natural motifs. A truncated form of IFABP (Delta 98 Delta) served to illustrate the nonintuitive notion that the integrity of the beta-barrel can indeed be compromised with no effect on the ability to attain a native-like fold. This is most likely the outcome of the key role played by the preservation of essential core residues. In the search for the minimal structural determinants of this fold, Delta 98 Delta offered room for further intervention. A dissection of this protein leads to a new abridged variant, Delta 78 Delta, containing 60% of the amino acids of IFABP. Spectroscopic analyses indicate that Delta 78 Delta retains substantial beta-sheet content and preserves tertiary interactions, displaying cooperative unfolding and binding activity. Most strikingly, this construct adopts a remarkably stable dimeric structure in solution. This phenomenon takes advantage of the inherent structural plasticity of this motif, likely profitting from edge-to-edge interactions between beta-sheets, whereas avoiding the most commonly occurring outcome represented by aggregation.
publishDate 2009
dc.date.none.fl_str_mv 2009-12
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/11336/25569
Franchini, Gisela Raquel; Curto, Lucrecia María; Caramelo, Julio Javier; Delfino, Jose Maria; Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding protein; Wiley; Protein Science; 18; 12; 12-2009; 2592-2602
0961-8368
1469-896X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25569
identifier_str_mv Franchini, Gisela Raquel; Curto, Lucrecia María; Caramelo, Julio Javier; Delfino, Jose Maria; Dissection of a beta-barrel motif leads to a functional dimer: the case of the intestinal fatty acid binding protein; Wiley; Protein Science; 18; 12; 12-2009; 2592-2602
0961-8368
1469-896X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/pro.273/abstract
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821277/
info:eu-repo/semantics/altIdentifier/doi/10.1002/pro.273
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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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