Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and function

Autores
Díaz Ludovico, Ivo; Gisonno, Romina Antonela; Tricerri, Maria Alejandra; Ramella, Nahuel; Garda, Horacio Alberto; Gonzalez, Marina Cecilia
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Human apolipoprotein A-I, the major protein fraction of the High density lipoproteins(HDL) has long been considered a protective factor against the development of coronaryheart disease. However, either the deletion of a residue (Lys 107) or a chronic proinflammatory scenario resulted in the deposition of the protein within atherosclerosisplaques and associated to amyloid deposits. The presence of protein aggregates in thislandscape may suggest that a shift from the native conformation should result in a lossof function. To elucidate whether structural changes may be responsible for the proteindeposition and misfunction, we compared by biophysical approaches the deletion mutantLys107-0 structure with respect to the protein with the native sequence (Wt), eitherfreshly resuspended or after controlled oxidation. A red shift in intrinsic Trp fluorescenceand a higher binding of Bis ANS indicate a more flexible structure of this mutant, whichpreserves lipid binding capacity. Structural flexibility seems to be clue to this role, as alower efficiency in intra-chain cross linking resulted in lower blockage of dimirystoylphosphatidyl choline (DMPC) clearance.In order to analyze the effect of oxidation on protein structure and function, Wt andLys107-0 were oxidized and protein structure reevaluated. Trp and Met oxidation isdetected by Mass Spec, and an increased tendency of the proteins to aggregate isobserved by microscopy approaches, which is especially evident for the deletion mutant.Nevertheless, lipid clearance and solubilization is not significantly modified, indicatingthat the integrity of the salt bridge network involving polar residues in the centraldomain of the protein is not essential to this function. More research will be done todetermine the importance of single residues in protein function.
Fil: Díaz Ludovico, Ivo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Gisonno, Romina Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Tricerri, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Ramella, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Garda, Horacio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Gonzalez, Marina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
XLVIII Reunión Anual de la Sociedad Argentina de Biofísica (SAB)
San Luis
Argentina
Sociedad Argentina de Biofísica
Materia
APOLIPOPROTEIN A-I
ATHEROSCLEROSIS
AMYLOIDOSIS
PROTEIN AGGREGATION
CROSSLINKING
PROTEIN OXYDATION
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:11336/277984
Acceder
id CONICETDig_b338c9ab9e510106fac192d24efb2733
oai_identifier_str oai:ri.conicet.gov.ar:11336/277984
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and functionDíaz Ludovico, IvoGisonno, Romina AntonelaTricerri, Maria AlejandraRamella, NahuelGarda, Horacio AlbertoGonzalez, Marina CeciliaAPOLIPOPROTEIN A-IATHEROSCLEROSISAMYLOIDOSISPROTEIN AGGREGATIONCROSSLINKINGPROTEIN OXYDATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Human apolipoprotein A-I, the major protein fraction of the High density lipoproteins(HDL) has long been considered a protective factor against the development of coronaryheart disease. However, either the deletion of a residue (Lys 107) or a chronic proinflammatory scenario resulted in the deposition of the protein within atherosclerosisplaques and associated to amyloid deposits. The presence of protein aggregates in thislandscape may suggest that a shift from the native conformation should result in a lossof function. To elucidate whether structural changes may be responsible for the proteindeposition and misfunction, we compared by biophysical approaches the deletion mutantLys107-0 structure with respect to the protein with the native sequence (Wt), eitherfreshly resuspended or after controlled oxidation. A red shift in intrinsic Trp fluorescenceand a higher binding of Bis ANS indicate a more flexible structure of this mutant, whichpreserves lipid binding capacity. Structural flexibility seems to be clue to this role, as alower efficiency in intra-chain cross linking resulted in lower blockage of dimirystoylphosphatidyl choline (DMPC) clearance.In order to analyze the effect of oxidation on protein structure and function, Wt andLys107-0 were oxidized and protein structure reevaluated. Trp and Met oxidation isdetected by Mass Spec, and an increased tendency of the proteins to aggregate isobserved by microscopy approaches, which is especially evident for the deletion mutant.Nevertheless, lipid clearance and solubilization is not significantly modified, indicatingthat the integrity of the salt bridge network involving polar residues in the centraldomain of the protein is not essential to this function. More research will be done todetermine the importance of single residues in protein function.Fil: Díaz Ludovico, Ivo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Gisonno, Romina Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Tricerri, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Ramella, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Garda, Horacio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Gonzalez, Marina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaXLVIII Reunión Anual de la Sociedad Argentina de Biofísica (SAB)San LuisArgentinaSociedad Argentina de BiofísicaSociedad Argentina de Biofísica2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/277984Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and function; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica (SAB); San Luis; Argentina; 2019; 180-1809789872759179CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://intranet.biofisica.org.ar/media/libro/libro_final_2019.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T13:36:09Zoai:ri.conicet.gov.ar:11336/277984instacron: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:34982025-12-23 13:36:10.181CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and function
title Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and function
spellingShingle Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and function
Díaz Ludovico, Ivo
APOLIPOPROTEIN A-I
ATHEROSCLEROSIS
AMYLOIDOSIS
PROTEIN AGGREGATION
CROSSLINKING
PROTEIN OXYDATION
title_short Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and function
title_full Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and function
title_fullStr Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and function
title_full_unstemmed Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and function
title_sort Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and function
dc.creator.none.fl_str_mv Díaz Ludovico, Ivo
Gisonno, Romina Antonela
Tricerri, Maria Alejandra
Ramella, Nahuel
Garda, Horacio Alberto
Gonzalez, Marina Cecilia
author Díaz Ludovico, Ivo
author_facet Díaz Ludovico, Ivo
Gisonno, Romina Antonela
Tricerri, Maria Alejandra
Ramella, Nahuel
Garda, Horacio Alberto
Gonzalez, Marina Cecilia
author_role author
author2 Gisonno, Romina Antonela
Tricerri, Maria Alejandra
Ramella, Nahuel
Garda, Horacio Alberto
Gonzalez, Marina Cecilia
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv APOLIPOPROTEIN A-I
ATHEROSCLEROSIS
AMYLOIDOSIS
PROTEIN AGGREGATION
CROSSLINKING
PROTEIN OXYDATION
topic APOLIPOPROTEIN A-I
ATHEROSCLEROSIS
AMYLOIDOSIS
PROTEIN AGGREGATION
CROSSLINKING
PROTEIN OXYDATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Human apolipoprotein A-I, the major protein fraction of the High density lipoproteins(HDL) has long been considered a protective factor against the development of coronaryheart disease. However, either the deletion of a residue (Lys 107) or a chronic proinflammatory scenario resulted in the deposition of the protein within atherosclerosisplaques and associated to amyloid deposits. The presence of protein aggregates in thislandscape may suggest that a shift from the native conformation should result in a lossof function. To elucidate whether structural changes may be responsible for the proteindeposition and misfunction, we compared by biophysical approaches the deletion mutantLys107-0 structure with respect to the protein with the native sequence (Wt), eitherfreshly resuspended or after controlled oxidation. A red shift in intrinsic Trp fluorescenceand a higher binding of Bis ANS indicate a more flexible structure of this mutant, whichpreserves lipid binding capacity. Structural flexibility seems to be clue to this role, as alower efficiency in intra-chain cross linking resulted in lower blockage of dimirystoylphosphatidyl choline (DMPC) clearance.In order to analyze the effect of oxidation on protein structure and function, Wt andLys107-0 were oxidized and protein structure reevaluated. Trp and Met oxidation isdetected by Mass Spec, and an increased tendency of the proteins to aggregate isobserved by microscopy approaches, which is especially evident for the deletion mutant.Nevertheless, lipid clearance and solubilization is not significantly modified, indicatingthat the integrity of the salt bridge network involving polar residues in the centraldomain of the protein is not essential to this function. More research will be done todetermine the importance of single residues in protein function.
Fil: Díaz Ludovico, Ivo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Gisonno, Romina Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Tricerri, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Ramella, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Garda, Horacio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Gonzalez, Marina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
XLVIII Reunión Anual de la Sociedad Argentina de Biofísica (SAB)
San Luis
Argentina
Sociedad Argentina de Biofísica
description Human apolipoprotein A-I, the major protein fraction of the High density lipoproteins(HDL) has long been considered a protective factor against the development of coronaryheart disease. However, either the deletion of a residue (Lys 107) or a chronic proinflammatory scenario resulted in the deposition of the protein within atherosclerosisplaques and associated to amyloid deposits. The presence of protein aggregates in thislandscape may suggest that a shift from the native conformation should result in a lossof function. To elucidate whether structural changes may be responsible for the proteindeposition and misfunction, we compared by biophysical approaches the deletion mutantLys107-0 structure with respect to the protein with the native sequence (Wt), eitherfreshly resuspended or after controlled oxidation. A red shift in intrinsic Trp fluorescenceand a higher binding of Bis ANS indicate a more flexible structure of this mutant, whichpreserves lipid binding capacity. Structural flexibility seems to be clue to this role, as alower efficiency in intra-chain cross linking resulted in lower blockage of dimirystoylphosphatidyl choline (DMPC) clearance.In order to analyze the effect of oxidation on protein structure and function, Wt andLys107-0 were oxidized and protein structure reevaluated. Trp and Met oxidation isdetected by Mass Spec, and an increased tendency of the proteins to aggregate isobserved by microscopy approaches, which is especially evident for the deletion mutant.Nevertheless, lipid clearance and solubilization is not significantly modified, indicatingthat the integrity of the salt bridge network involving polar residues in the centraldomain of the protein is not essential to this function. More research will be done todetermine the importance of single residues in protein function.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/277984
Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and function; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica (SAB); San Luis; Argentina; 2019; 180-180
9789872759179
CONICET Digital
CONICET
url http://hdl.handle.net/11336/277984
identifier_str_mv Folding of a natural variant of human apolipoprotein A-I associated with atherosclerosis. Micro environment and function; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica (SAB); San Luis; Argentina; 2019; 180-180
9789872759179
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://intranet.biofisica.org.ar/media/libro/libro_final_2019.pdf
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
application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Biofísica
publisher.none.fl_str_mv Sociedad Argentina de Biofísica
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_ 1852335248244736000
score 12.952241

Publicaciones similares