Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.

Autores
Díaz Ludovico, Ivo; Bedi, Shimpi; Melchior, John; Gonzalez, Marina Cecilia; Garda, Horacio Alberto; Davidson, Sean
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Human apolipoprotein (apo)A-I is the primarily protein component of high-density lipoproteins (HDL) where it plays a pivotal role in governing HDL metabolism. The deletion mutant Lys107del (∆K107) is a natural variant of apoA-I which is associated with hypertriglyceridemia and accelerated atherosclerosis in carriers. While the impact of ∆K107 on HDL metabolism and cardiovascular disease has been extensively studied, little information exists on the structural mechanisms resulting in the observed phenotypes. The purpose of this study was to investigate and identify the structural differences between wild-type (Wt) and ∆K107 apoA-I driving the dysfunctional lipoprotein metabolism observed in the carriers. Chemical cross-linking was used to capture monomeric, dimeric, trimeric, and tetrameric Wt and ∆K107 apoA-I. SDS-PAGE showed a shift in distribution of the oligomeric species with ∆K107 existing primarily as a monomer compared to Wt apoA-I. Respective species were isolated by size exclusion chromatography which confirmed the observed differences in the distribution of the oligomeric species. No significant differences were observed in fluorescence measurements between oligomers in Wt or ∆K107 apoA-I indicating similar environments for Trp residues. Respective species were subjected to liquid chromatography-mass spectrometry (LC-MS) to determine differences in the cross-linking pattern between the respective oligomers of Wt and ∆K107 apoA-I. Using a combination of SimXL and quantitative cross-linking, we observed a shift in the abundance of cross-links between residues 140-239, 140-118, 226-182, 208-118, 23-59. Our work indicates that ∆K107 preferentially exists as a monomer in solution and cross-linking shows differences in the structural conformation of ∆K107 compared to Wt apoA-I. These observed structural changes may contribute to the observed phenotypes in carriers of ∆K107 .
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: Bedi, Shimpi. University of Cincinnati; Estados Unidos
Fil: Melchior, John. University of Cincinnati; Estados Unidos
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
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: Davidson, Sean. University of Cincinnati; Estados Unidos
Vascular Discovery: From Genes to Medicine Scientific Sessions 2020
Estados Unidos
American Heart Association
Materia
apolipoprotein A-I
Deletion mutant Lys 107
self-associate
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:11336/278254
Acceder
id CONICETDig_c523934ee217c9ae0cb868c3de39f246
oai_identifier_str oai:ri.conicet.gov.ar:11336/278254
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.Díaz Ludovico, IvoBedi, ShimpiMelchior, JohnGonzalez, Marina CeciliaGarda, Horacio AlbertoDavidson, Seanapolipoprotein A-IDeletion mutant Lys 107self-associatehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Human apolipoprotein (apo)A-I is the primarily protein component of high-density lipoproteins (HDL) where it plays a pivotal role in governing HDL metabolism. The deletion mutant Lys107del (∆K107) is a natural variant of apoA-I which is associated with hypertriglyceridemia and accelerated atherosclerosis in carriers. While the impact of ∆K107 on HDL metabolism and cardiovascular disease has been extensively studied, little information exists on the structural mechanisms resulting in the observed phenotypes. The purpose of this study was to investigate and identify the structural differences between wild-type (Wt) and ∆K107 apoA-I driving the dysfunctional lipoprotein metabolism observed in the carriers. Chemical cross-linking was used to capture monomeric, dimeric, trimeric, and tetrameric Wt and ∆K107 apoA-I. SDS-PAGE showed a shift in distribution of the oligomeric species with ∆K107 existing primarily as a monomer compared to Wt apoA-I. Respective species were isolated by size exclusion chromatography which confirmed the observed differences in the distribution of the oligomeric species. No significant differences were observed in fluorescence measurements between oligomers in Wt or ∆K107 apoA-I indicating similar environments for Trp residues. Respective species were subjected to liquid chromatography-mass spectrometry (LC-MS) to determine differences in the cross-linking pattern between the respective oligomers of Wt and ∆K107 apoA-I. Using a combination of SimXL and quantitative cross-linking, we observed a shift in the abundance of cross-links between residues 140-239, 140-118, 226-182, 208-118, 23-59. Our work indicates that ∆K107 preferentially exists as a monomer in solution and cross-linking shows differences in the structural conformation of ∆K107 compared to Wt apoA-I. These observed structural changes may contribute to the observed phenotypes in carriers of ∆K107 .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: Bedi, Shimpi. University of Cincinnati; Estados UnidosFil: Melchior, John. University of Cincinnati; Estados UnidosFil: 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"; 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: Davidson, Sean. University of Cincinnati; Estados UnidosVascular Discovery: From Genes to Medicine Scientific Sessions 2020Estados UnidosAmerican Heart AssociationAmerican Heart Association's Vascular Discovery2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/278254Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.; Vascular Discovery: From Genes to Medicine Scientific Sessions 2020; Estados Unidos; 2020; 1-1CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ahajournals.org/doi/10.1161/atvb.40.suppl_1.207Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T13:45:12Zoai:ri.conicet.gov.ar:11336/278254instacron: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 13:45:12.683CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.
title Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.
spellingShingle Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.
Díaz Ludovico, Ivo
apolipoprotein A-I
Deletion mutant Lys 107
self-associate
title_short Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.
title_full Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.
title_fullStr Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.
title_full_unstemmed Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.
title_sort Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.
dc.creator.none.fl_str_mv Díaz Ludovico, Ivo
Bedi, Shimpi
Melchior, John
Gonzalez, Marina Cecilia
Garda, Horacio Alberto
Davidson, Sean
author Díaz Ludovico, Ivo
author_facet Díaz Ludovico, Ivo
Bedi, Shimpi
Melchior, John
Gonzalez, Marina Cecilia
Garda, Horacio Alberto
Davidson, Sean
author_role author
author2 Bedi, Shimpi
Melchior, John
Gonzalez, Marina Cecilia
Garda, Horacio Alberto
Davidson, Sean
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv apolipoprotein A-I
Deletion mutant Lys 107
self-associate
topic apolipoprotein A-I
Deletion mutant Lys 107
self-associate
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 (apo)A-I is the primarily protein component of high-density lipoproteins (HDL) where it plays a pivotal role in governing HDL metabolism. The deletion mutant Lys107del (∆K107) is a natural variant of apoA-I which is associated with hypertriglyceridemia and accelerated atherosclerosis in carriers. While the impact of ∆K107 on HDL metabolism and cardiovascular disease has been extensively studied, little information exists on the structural mechanisms resulting in the observed phenotypes. The purpose of this study was to investigate and identify the structural differences between wild-type (Wt) and ∆K107 apoA-I driving the dysfunctional lipoprotein metabolism observed in the carriers. Chemical cross-linking was used to capture monomeric, dimeric, trimeric, and tetrameric Wt and ∆K107 apoA-I. SDS-PAGE showed a shift in distribution of the oligomeric species with ∆K107 existing primarily as a monomer compared to Wt apoA-I. Respective species were isolated by size exclusion chromatography which confirmed the observed differences in the distribution of the oligomeric species. No significant differences were observed in fluorescence measurements between oligomers in Wt or ∆K107 apoA-I indicating similar environments for Trp residues. Respective species were subjected to liquid chromatography-mass spectrometry (LC-MS) to determine differences in the cross-linking pattern between the respective oligomers of Wt and ∆K107 apoA-I. Using a combination of SimXL and quantitative cross-linking, we observed a shift in the abundance of cross-links between residues 140-239, 140-118, 226-182, 208-118, 23-59. Our work indicates that ∆K107 preferentially exists as a monomer in solution and cross-linking shows differences in the structural conformation of ∆K107 compared to Wt apoA-I. These observed structural changes may contribute to the observed phenotypes in carriers of ∆K107 .
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: Bedi, Shimpi. University of Cincinnati; Estados Unidos
Fil: Melchior, John. University of Cincinnati; Estados Unidos
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
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: Davidson, Sean. University of Cincinnati; Estados Unidos
Vascular Discovery: From Genes to Medicine Scientific Sessions 2020
Estados Unidos
American Heart Association
description Human apolipoprotein (apo)A-I is the primarily protein component of high-density lipoproteins (HDL) where it plays a pivotal role in governing HDL metabolism. The deletion mutant Lys107del (∆K107) is a natural variant of apoA-I which is associated with hypertriglyceridemia and accelerated atherosclerosis in carriers. While the impact of ∆K107 on HDL metabolism and cardiovascular disease has been extensively studied, little information exists on the structural mechanisms resulting in the observed phenotypes. The purpose of this study was to investigate and identify the structural differences between wild-type (Wt) and ∆K107 apoA-I driving the dysfunctional lipoprotein metabolism observed in the carriers. Chemical cross-linking was used to capture monomeric, dimeric, trimeric, and tetrameric Wt and ∆K107 apoA-I. SDS-PAGE showed a shift in distribution of the oligomeric species with ∆K107 existing primarily as a monomer compared to Wt apoA-I. Respective species were isolated by size exclusion chromatography which confirmed the observed differences in the distribution of the oligomeric species. No significant differences were observed in fluorescence measurements between oligomers in Wt or ∆K107 apoA-I indicating similar environments for Trp residues. Respective species were subjected to liquid chromatography-mass spectrometry (LC-MS) to determine differences in the cross-linking pattern between the respective oligomers of Wt and ∆K107 apoA-I. Using a combination of SimXL and quantitative cross-linking, we observed a shift in the abundance of cross-links between residues 140-239, 140-118, 226-182, 208-118, 23-59. Our work indicates that ∆K107 preferentially exists as a monomer in solution and cross-linking shows differences in the structural conformation of ∆K107 compared to Wt apoA-I. These observed structural changes may contribute to the observed phenotypes in carriers of ∆K107 .
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
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/11336/278254
Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.; Vascular Discovery: From Genes to Medicine Scientific Sessions 2020; Estados Unidos; 2020; 1-1
CONICET Digital
CONICET
url http://hdl.handle.net/11336/278254
identifier_str_mv Deletion of Lys 107 modify the ability of apoA-I to self-associate in solution.; Vascular Discovery: From Genes to Medicine Scientific Sessions 2020; Estados Unidos; 2020; 1-1
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.ahajournals.org/doi/10.1161/atvb.40.suppl_1.207
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/vnd.openxmlformats-officedocument.wordprocessingml.document
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv American Heart Association's Vascular Discovery
publisher.none.fl_str_mv American Heart Association's Vascular Discovery
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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