Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-I

Autores
Díaz Ludovico, Ivo; Geh, Esmond; 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 A-I (apoA-I) is the major protein component of high-density lipoproteins (HDLs) that plays a pivotal role in lipoprotein metabolism. The deletion mutant Lys107del (ΔK107) it’s a natural variant of apoA-I (Wt) related to early atherosclerosis and hypertriglyceridemia in carriers. While this mutant has been extensively studied, little information exists on the structural and functional basis for this phenotype. To investigate if exists alterations in oligomeric states of ΔK107 that are involved in his pathogenicity, we used isolated BS3-crosslinked oligomers (XL-oligomer) to investigate its structure and functionality in comparison with the Wt. Fluorescence measurements in monomeric, dimeric, trimeric and tetrameric Wt apoA-I showed highly similar spectra indicating similar environments for Trp residues. ΔK107 exhibited a slight red shift, likely due to the Lys deletion near a Try residue, but also showed similar spectra in all oligomeric states. Upon incorporation into lipoprotein complexes, the same red shift has been observed in all oligomeric states of ΔK107. Native PAGE sizing of XL-oligomers and XL-oligomer-lipoprotein complexes showed a comparable distribution for both variants. All XL-oligomers form large (440-660KDa) lipoprotein complexes with DMPC; but not all could form the typical small (140KDa) lipoprotein complexes observed for uncrosslinked proteins. Native LDL (nLDL) binding assays showed no-differences between Wt and ΔK107 in the profile and the amount of protein bind to the LDL. ΔK107 has been previously proposed to alter LDL or VLDL lipolysis by binding to these lipoproteins and altering lipolysis. Our work shows that the physiological effects of the mutation are likely not related with both their capacity to form Wt-same size oligomers or the capacity to interact with lipids.
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: Geh, Esmond. Cincinnati Childrens Hospital; Estados Unidos
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
American Heart Association's Vascular Discovery: From Genes to Medicine 2020 Scientific Sessions
Estados Unidos
American Heart Association
Materia
apolipoprotein A-I
deletion mutant Lys107del
lipoprotein complexes
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:11336/278023
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/278023
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-IDíaz Ludovico, IvoGeh, EsmondBedi, ShimpiMelchior, JohnGonzalez, Marina CeciliaGarda, Horacio AlbertoDavidson, Seanapolipoprotein A-Ideletion mutant Lys107dellipoprotein complexeshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Human apolipoprotein A-I (apoA-I) is the major protein component of high-density lipoproteins (HDLs) that plays a pivotal role in lipoprotein metabolism. The deletion mutant Lys107del (ΔK107) it’s a natural variant of apoA-I (Wt) related to early atherosclerosis and hypertriglyceridemia in carriers. While this mutant has been extensively studied, little information exists on the structural and functional basis for this phenotype. To investigate if exists alterations in oligomeric states of ΔK107 that are involved in his pathogenicity, we used isolated BS3-crosslinked oligomers (XL-oligomer) to investigate its structure and functionality in comparison with the Wt. Fluorescence measurements in monomeric, dimeric, trimeric and tetrameric Wt apoA-I showed highly similar spectra indicating similar environments for Trp residues. ΔK107 exhibited a slight red shift, likely due to the Lys deletion near a Try residue, but also showed similar spectra in all oligomeric states. Upon incorporation into lipoprotein complexes, the same red shift has been observed in all oligomeric states of ΔK107. Native PAGE sizing of XL-oligomers and XL-oligomer-lipoprotein complexes showed a comparable distribution for both variants. All XL-oligomers form large (440-660KDa) lipoprotein complexes with DMPC; but not all could form the typical small (140KDa) lipoprotein complexes observed for uncrosslinked proteins. Native LDL (nLDL) binding assays showed no-differences between Wt and ΔK107 in the profile and the amount of protein bind to the LDL. ΔK107 has been previously proposed to alter LDL or VLDL lipolysis by binding to these lipoproteins and altering lipolysis. Our work shows that the physiological effects of the mutation are likely not related with both their capacity to form Wt-same size oligomers or the capacity to interact with lipids.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: Geh, Esmond. Cincinnati Childrens Hospital; Estados UnidosFil: 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 UnidosAmerican Heart Association's Vascular Discovery: From Genes to Medicine 2020 Scientific SessionsEstados UnidosAmerican Heart AssociationAmerican Heart Association's Vascular Discovery2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/278023Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-I; American Heart Association's Vascular Discovery: From Genes to Medicine 2020 Scientific Sessions; Estados Unidos; 2020; 1-1CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ahajournals.org/doi/10.1161/atvb.40.suppl_1.201Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T13:12:30Zoai:ri.conicet.gov.ar:11336/278023instacron: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 13:12:30.74CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-I
title Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-I
spellingShingle Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-I
Díaz Ludovico, Ivo
apolipoprotein A-I
deletion mutant Lys107del
lipoprotein complexes
title_short Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-I
title_full Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-I
title_fullStr Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-I
title_full_unstemmed Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-I
title_sort Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-I
dc.creator.none.fl_str_mv Díaz Ludovico, Ivo
Geh, Esmond
Bedi, Shimpi
Melchior, John
Gonzalez, Marina Cecilia
Garda, Horacio Alberto
Davidson, Sean
author Díaz Ludovico, Ivo
author_facet Díaz Ludovico, Ivo
Geh, Esmond
Bedi, Shimpi
Melchior, John
Gonzalez, Marina Cecilia
Garda, Horacio Alberto
Davidson, Sean
author_role author
author2 Geh, Esmond
Bedi, Shimpi
Melchior, John
Gonzalez, Marina Cecilia
Garda, Horacio Alberto
Davidson, Sean
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv apolipoprotein A-I
deletion mutant Lys107del
lipoprotein complexes
topic apolipoprotein A-I
deletion mutant Lys107del
lipoprotein complexes
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 (apoA-I) is the major protein component of high-density lipoproteins (HDLs) that plays a pivotal role in lipoprotein metabolism. The deletion mutant Lys107del (ΔK107) it’s a natural variant of apoA-I (Wt) related to early atherosclerosis and hypertriglyceridemia in carriers. While this mutant has been extensively studied, little information exists on the structural and functional basis for this phenotype. To investigate if exists alterations in oligomeric states of ΔK107 that are involved in his pathogenicity, we used isolated BS3-crosslinked oligomers (XL-oligomer) to investigate its structure and functionality in comparison with the Wt. Fluorescence measurements in monomeric, dimeric, trimeric and tetrameric Wt apoA-I showed highly similar spectra indicating similar environments for Trp residues. ΔK107 exhibited a slight red shift, likely due to the Lys deletion near a Try residue, but also showed similar spectra in all oligomeric states. Upon incorporation into lipoprotein complexes, the same red shift has been observed in all oligomeric states of ΔK107. Native PAGE sizing of XL-oligomers and XL-oligomer-lipoprotein complexes showed a comparable distribution for both variants. All XL-oligomers form large (440-660KDa) lipoprotein complexes with DMPC; but not all could form the typical small (140KDa) lipoprotein complexes observed for uncrosslinked proteins. Native LDL (nLDL) binding assays showed no-differences between Wt and ΔK107 in the profile and the amount of protein bind to the LDL. ΔK107 has been previously proposed to alter LDL or VLDL lipolysis by binding to these lipoproteins and altering lipolysis. Our work shows that the physiological effects of the mutation are likely not related with both their capacity to form Wt-same size oligomers or the capacity to interact with lipids.
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: Geh, Esmond. Cincinnati Childrens Hospital; Estados Unidos
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
American Heart Association's Vascular Discovery: From Genes to Medicine 2020 Scientific Sessions
Estados Unidos
American Heart Association
description Human apolipoprotein A-I (apoA-I) is the major protein component of high-density lipoproteins (HDLs) that plays a pivotal role in lipoprotein metabolism. The deletion mutant Lys107del (ΔK107) it’s a natural variant of apoA-I (Wt) related to early atherosclerosis and hypertriglyceridemia in carriers. While this mutant has been extensively studied, little information exists on the structural and functional basis for this phenotype. To investigate if exists alterations in oligomeric states of ΔK107 that are involved in his pathogenicity, we used isolated BS3-crosslinked oligomers (XL-oligomer) to investigate its structure and functionality in comparison with the Wt. Fluorescence measurements in monomeric, dimeric, trimeric and tetrameric Wt apoA-I showed highly similar spectra indicating similar environments for Trp residues. ΔK107 exhibited a slight red shift, likely due to the Lys deletion near a Try residue, but also showed similar spectra in all oligomeric states. Upon incorporation into lipoprotein complexes, the same red shift has been observed in all oligomeric states of ΔK107. Native PAGE sizing of XL-oligomers and XL-oligomer-lipoprotein complexes showed a comparable distribution for both variants. All XL-oligomers form large (440-660KDa) lipoprotein complexes with DMPC; but not all could form the typical small (140KDa) lipoprotein complexes observed for uncrosslinked proteins. Native LDL (nLDL) binding assays showed no-differences between Wt and ΔK107 in the profile and the amount of protein bind to the LDL. ΔK107 has been previously proposed to alter LDL or VLDL lipolysis by binding to these lipoproteins and altering lipolysis. Our work shows that the physiological effects of the mutation are likely not related with both their capacity to form Wt-same size oligomers or the capacity to interact with lipids.
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
Journal
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/11336/278023
Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-I; American Heart Association's Vascular Discovery: From Genes to Medicine 2020 Scientific Sessions; Estados Unidos; 2020; 1-1
CONICET Digital
CONICET
url http://hdl.handle.net/11336/278023
identifier_str_mv Naturally Occurring Deletion of Lys 107 Does Not Alter Lipid Binding Affinity of Apolipoprotein A-I; American Heart Association's Vascular Discovery: From Genes to Medicine 2020 Scientific Sessions; 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_1.201
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
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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