Molecular basis for the protective effects of low-density lipoprotein receptor-related protein 1 (LRP1)-derived peptides against LDL aggregation

Aggregated LDL is the first ligand reported to interact with the cluster II CR9 domain of low-density lipoprotein receptor-related protein 1 (LRP1). In particular, the C-terminal half of domain CR9, comprising the region Gly(1127)-Cys(1140) exclusively recognizes aggregated LDL and it is crucial for...

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Authors: Benitez-Arnaro, A, Pallara, C, Nasarre, L, Rivas-Urbina, A, Benitez, S, Vea, A, Bornachea, O, de Gonzalo-Calvo, D, Serra-Mir, G, Villegas, S, Prades, R, Sanchez-Quesada, JL, Chiva, C, Sabido, E, Tarrago, T, Llorente-Cortes, V
Format: article
Status:Published version
Publication Date:2019
Country:España
Institution:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repository:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p2584
Online Access:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2584
Access Level:Open access
Keyword:Lipoprotein aggregation
LRP1-derived peptides
ApoB-100
SMase, PLA(2), atherosclerosis
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spelling Molecular basis for the protective effects of low-density lipoprotein receptor-related protein 1 (LRP1)-derived peptides against LDL aggregationBenitez-Arnaro, APallara, CNasarre, LRivas-Urbina, ABenitez, SVea, ABornachea, Ode Gonzalo-Calvo, DSerra-Mir, GVillegas, SPrades, RSanchez-Quesada, JLChiva, CSabido, ETarrago, TLlorente-Cortes, VLipoprotein aggregationLRP1-derived peptidesApoB-100SMase, PLA(2), atherosclerosisAggregated LDL is the first ligand reported to interact with the cluster II CR9 domain of low-density lipoprotein receptor-related protein 1 (LRP1). In particular, the C-terminal half of domain CR9, comprising the region Gly(1127)-Cys(1140) exclusively recognizes aggregated LDL and it is crucial for aggregated LDL binding. Our aim was to study the effect of the sequence Gly(1127)-Cys(1140) (named peptide LP3 and its retro-enantio version, named peptide DP3) on the structural characteristics of sphingomyelinase- (SMase) and phospholipase 2 (PLA(2))-modified LDL particles. Turbidimetry, gel filtration chromatography (GFC) and transmission electronic microscopy (TEM) analysis showed that LP3 and DP3 peptides strongly inhibited SMase- and PLA(2)-induced LDL aggregation. Nondenaturing polyacrylamide gradient gel electrophoresis (GGE), agarose gel electrophoresis and high-performance thin-layer chromatography (HPTLC) indicated that LP3 and DP3 prevented SMase-induced alterations in LDL particle size, electric charge and phospholipid content, respectively, but not those induced by PLA(2). Western blot analysis showed that LP3 and DP3 counteracted changes in ApoB-100 conformation induced by the two enzymes. LDL proteomics (LDL trypsin digestion followed by mass spectroscopy) and computational modeling methods evidenced that peptides preserve ApoB-100 conformation due to their electrostatic interactions with a basic region of ApoB-100. These results demonstrate that LRP1-derived peptides are protective against LDL aggregation, even in conditions of extreme lipolysis, through their capacity to bind to ApoB-100 regions critical for ApoB-100 conformational preservation. These results suggests that these LRP1(CR9) derived peptides could be promising tools to prevent LDL aggregation induced by the main proteolytic enzymes acting in the arterial intima.ELSEVIER SCIENCE BV2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2584BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANESISSN: 00052736ISSNe: 18792642reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Holandésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p25842026-06-14T12:41:47Z
dc.title.none.fl_str_mv Molecular basis for the protective effects of low-density lipoprotein receptor-related protein 1 (LRP1)-derived peptides against LDL aggregation
title Molecular basis for the protective effects of low-density lipoprotein receptor-related protein 1 (LRP1)-derived peptides against LDL aggregation
spellingShingle Molecular basis for the protective effects of low-density lipoprotein receptor-related protein 1 (LRP1)-derived peptides against LDL aggregation
Benitez-Arnaro, A
Lipoprotein aggregation
LRP1-derived peptides
ApoB-100
SMase, PLA(2), atherosclerosis
title_short Molecular basis for the protective effects of low-density lipoprotein receptor-related protein 1 (LRP1)-derived peptides against LDL aggregation
title_full Molecular basis for the protective effects of low-density lipoprotein receptor-related protein 1 (LRP1)-derived peptides against LDL aggregation
title_fullStr Molecular basis for the protective effects of low-density lipoprotein receptor-related protein 1 (LRP1)-derived peptides against LDL aggregation
title_full_unstemmed Molecular basis for the protective effects of low-density lipoprotein receptor-related protein 1 (LRP1)-derived peptides against LDL aggregation
title_sort Molecular basis for the protective effects of low-density lipoprotein receptor-related protein 1 (LRP1)-derived peptides against LDL aggregation
dc.creator.none.fl_str_mv Benitez-Arnaro, A
Pallara, C
Nasarre, L
Rivas-Urbina, A
Benitez, S
Vea, A
Bornachea, O
de Gonzalo-Calvo, D
Serra-Mir, G
Villegas, S
Prades, R
Sanchez-Quesada, JL
Chiva, C
Sabido, E
Tarrago, T
Llorente-Cortes, V
author Benitez-Arnaro, A
author_facet Benitez-Arnaro, A
Pallara, C
Nasarre, L
Rivas-Urbina, A
Benitez, S
Vea, A
Bornachea, O
de Gonzalo-Calvo, D
Serra-Mir, G
Villegas, S
Prades, R
Sanchez-Quesada, JL
Chiva, C
Sabido, E
Tarrago, T
Llorente-Cortes, V
author_role author
author2 Pallara, C
Nasarre, L
Rivas-Urbina, A
Benitez, S
Vea, A
Bornachea, O
de Gonzalo-Calvo, D
Serra-Mir, G
Villegas, S
Prades, R
Sanchez-Quesada, JL
Chiva, C
Sabido, E
Tarrago, T
Llorente-Cortes, V
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Lipoprotein aggregation
LRP1-derived peptides
ApoB-100
SMase, PLA(2), atherosclerosis
topic Lipoprotein aggregation
LRP1-derived peptides
ApoB-100
SMase, PLA(2), atherosclerosis
description Aggregated LDL is the first ligand reported to interact with the cluster II CR9 domain of low-density lipoprotein receptor-related protein 1 (LRP1). In particular, the C-terminal half of domain CR9, comprising the region Gly(1127)-Cys(1140) exclusively recognizes aggregated LDL and it is crucial for aggregated LDL binding. Our aim was to study the effect of the sequence Gly(1127)-Cys(1140) (named peptide LP3 and its retro-enantio version, named peptide DP3) on the structural characteristics of sphingomyelinase- (SMase) and phospholipase 2 (PLA(2))-modified LDL particles. Turbidimetry, gel filtration chromatography (GFC) and transmission electronic microscopy (TEM) analysis showed that LP3 and DP3 peptides strongly inhibited SMase- and PLA(2)-induced LDL aggregation. Nondenaturing polyacrylamide gradient gel electrophoresis (GGE), agarose gel electrophoresis and high-performance thin-layer chromatography (HPTLC) indicated that LP3 and DP3 prevented SMase-induced alterations in LDL particle size, electric charge and phospholipid content, respectively, but not those induced by PLA(2). Western blot analysis showed that LP3 and DP3 counteracted changes in ApoB-100 conformation induced by the two enzymes. LDL proteomics (LDL trypsin digestion followed by mass spectroscopy) and computational modeling methods evidenced that peptides preserve ApoB-100 conformation due to their electrostatic interactions with a basic region of ApoB-100. These results demonstrate that LRP1-derived peptides are protective against LDL aggregation, even in conditions of extreme lipolysis, through their capacity to bind to ApoB-100 regions critical for ApoB-100 conformational preservation. These results suggests that these LRP1(CR9) derived peptides could be promising tools to prevent LDL aggregation induced by the main proteolytic enzymes acting in the arterial intima.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2584
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2584
dc.language.none.fl_str_mv Holandés
language_invalid_str_mv Holandés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER SCIENCE BV
publisher.none.fl_str_mv ELSEVIER SCIENCE BV
dc.source.none.fl_str_mv BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
ISSN: 00052736
ISSNe: 18792642
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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