Understanding the role of apolipoproteinA-I in atherosclerosis : Posttranslational modifications synergize dysfunction?
- Autores
- Díaz Ludovico, Ivo; Gisonno, Romina Antonela; González, Marina Cecilia; Garda, Horacio Alberto; Ramella, Nahuel Alberto; Tricerri, María Alejandra
- Año de publicación
- 2021
- Idioma
- español castellano
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background: The identification of dysfunctional human apolipoprotein A-I (apoA-I) in atherosclerotic plaques suggests that protein structure and function may be hampered under a chronic pro inflammatory scenario. Moreover, the fact that natural mutants of this protein elicit severe cardiovascular diseases (CVD) strongly indicates that the native folding could shift due to the mutation, yielding a structure more prone to misfold or misfunction. To understand the events that determine the failure of apoA-I structural flexibility to fulfill its protective role, we took advantage of the study of a natural variant with a deletion of the residue lysine 107 (K107del) associated with atherosclerosis. Methods: Biophysical approaches, such as electrophoresis, fluorescence and spectroscopy were used to characterize proteins structure and function, either in native conformation or under oxidation or intramolecular crosslinking. Results: K107del structure was more flexible than the protein with the native sequence (Wt) but interactions with artificial membranes were preserved. Instead, structural restrictions by intramolecular crosslinking impaired the Wt and K107del lipid solubilization function. In addition, controlled oxidation decreased the yield of the native dimer conformation for both variants. Conclusions: We conclude that even though mutations may alter protein structure and spatial arrangement, the highly flexible conformation compensates the mild shift from the native folding. Instead, post translational apoAI modifications (probably chronic and progressive) are required to raise a protein conformation with significant loss of function and increased aggregation tendency. General significance: The results learnt from this variant strength a close association between amyloidosis and atherosclerosis.
Instituto de Investigaciones Bioquímicas de La Plata
Facultad de Ciencias Médicas - Materia
-
Ciencias Médicas
Atherosclerosis
Apolipoprotein A-I
K107del natural variant
Protein misfolding
Amyloidosis
Inflammation - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by-nc-nd/4.0/
- Repositorio
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/124995
Ver los metadatos del registro completo
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Understanding the role of apolipoproteinA-I in atherosclerosis : Posttranslational modifications synergize dysfunction?Díaz Ludovico, IvoGisonno, Romina AntonelaGonzález, Marina CeciliaGarda, Horacio AlbertoRamella, Nahuel AlbertoTricerri, María AlejandraCiencias MédicasAtherosclerosisApolipoprotein A-IK107del natural variantProtein misfoldingAmyloidosisInflammationBackground: The identification of dysfunctional human apolipoprotein A-I (apoA-I) in atherosclerotic plaques suggests that protein structure and function may be hampered under a chronic pro inflammatory scenario. Moreover, the fact that natural mutants of this protein elicit severe cardiovascular diseases (CVD) strongly indicates that the native folding could shift due to the mutation, yielding a structure more prone to misfold or misfunction. To understand the events that determine the failure of apoA-I structural flexibility to fulfill its protective role, we took advantage of the study of a natural variant with a deletion of the residue lysine 107 (K107del) associated with atherosclerosis. Methods: Biophysical approaches, such as electrophoresis, fluorescence and spectroscopy were used to characterize proteins structure and function, either in native conformation or under oxidation or intramolecular crosslinking. Results: K107del structure was more flexible than the protein with the native sequence (Wt) but interactions with artificial membranes were preserved. Instead, structural restrictions by intramolecular crosslinking impaired the Wt and K107del lipid solubilization function. In addition, controlled oxidation decreased the yield of the native dimer conformation for both variants. Conclusions: We conclude that even though mutations may alter protein structure and spatial arrangement, the highly flexible conformation compensates the mild shift from the native folding. Instead, post translational apoAI modifications (probably chronic and progressive) are required to raise a protein conformation with significant loss of function and increased aggregation tendency. General significance: The results learnt from this variant strength a close association between amyloidosis and atherosclerosis.Instituto de Investigaciones Bioquímicas de La PlataFacultad de Ciencias Médicas2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/124995spainfo:eu-repo/semantics/altIdentifier/issn/0304-4165/info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbagen.2020.129732info:eu-repo/semantics/reference/hdl/10915/124884info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-15T11:21:57Zoai:sedici.unlp.edu.ar:10915/124995Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-15 11:21:57.54SEDICI (UNLP) - Universidad Nacional de La Platafalse |
dc.title.none.fl_str_mv |
Understanding the role of apolipoproteinA-I in atherosclerosis : Posttranslational modifications synergize dysfunction? |
title |
Understanding the role of apolipoproteinA-I in atherosclerosis : Posttranslational modifications synergize dysfunction? |
spellingShingle |
Understanding the role of apolipoproteinA-I in atherosclerosis : Posttranslational modifications synergize dysfunction? Díaz Ludovico, Ivo Ciencias Médicas Atherosclerosis Apolipoprotein A-I K107del natural variant Protein misfolding Amyloidosis Inflammation |
title_short |
Understanding the role of apolipoproteinA-I in atherosclerosis : Posttranslational modifications synergize dysfunction? |
title_full |
Understanding the role of apolipoproteinA-I in atherosclerosis : Posttranslational modifications synergize dysfunction? |
title_fullStr |
Understanding the role of apolipoproteinA-I in atherosclerosis : Posttranslational modifications synergize dysfunction? |
title_full_unstemmed |
Understanding the role of apolipoproteinA-I in atherosclerosis : Posttranslational modifications synergize dysfunction? |
title_sort |
Understanding the role of apolipoproteinA-I in atherosclerosis : Posttranslational modifications synergize dysfunction? |
dc.creator.none.fl_str_mv |
Díaz Ludovico, Ivo Gisonno, Romina Antonela González, Marina Cecilia Garda, Horacio Alberto Ramella, Nahuel Alberto Tricerri, María Alejandra |
author |
Díaz Ludovico, Ivo |
author_facet |
Díaz Ludovico, Ivo Gisonno, Romina Antonela González, Marina Cecilia Garda, Horacio Alberto Ramella, Nahuel Alberto Tricerri, María Alejandra |
author_role |
author |
author2 |
Gisonno, Romina Antonela González, Marina Cecilia Garda, Horacio Alberto Ramella, Nahuel Alberto Tricerri, María Alejandra |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
Ciencias Médicas Atherosclerosis Apolipoprotein A-I K107del natural variant Protein misfolding Amyloidosis Inflammation |
topic |
Ciencias Médicas Atherosclerosis Apolipoprotein A-I K107del natural variant Protein misfolding Amyloidosis Inflammation |
dc.description.none.fl_txt_mv |
Background: The identification of dysfunctional human apolipoprotein A-I (apoA-I) in atherosclerotic plaques suggests that protein structure and function may be hampered under a chronic pro inflammatory scenario. Moreover, the fact that natural mutants of this protein elicit severe cardiovascular diseases (CVD) strongly indicates that the native folding could shift due to the mutation, yielding a structure more prone to misfold or misfunction. To understand the events that determine the failure of apoA-I structural flexibility to fulfill its protective role, we took advantage of the study of a natural variant with a deletion of the residue lysine 107 (K107del) associated with atherosclerosis. Methods: Biophysical approaches, such as electrophoresis, fluorescence and spectroscopy were used to characterize proteins structure and function, either in native conformation or under oxidation or intramolecular crosslinking. Results: K107del structure was more flexible than the protein with the native sequence (Wt) but interactions with artificial membranes were preserved. Instead, structural restrictions by intramolecular crosslinking impaired the Wt and K107del lipid solubilization function. In addition, controlled oxidation decreased the yield of the native dimer conformation for both variants. Conclusions: We conclude that even though mutations may alter protein structure and spatial arrangement, the highly flexible conformation compensates the mild shift from the native folding. Instead, post translational apoAI modifications (probably chronic and progressive) are required to raise a protein conformation with significant loss of function and increased aggregation tendency. General significance: The results learnt from this variant strength a close association between amyloidosis and atherosclerosis. Instituto de Investigaciones Bioquímicas de La Plata Facultad de Ciencias Médicas |
description |
Background: The identification of dysfunctional human apolipoprotein A-I (apoA-I) in atherosclerotic plaques suggests that protein structure and function may be hampered under a chronic pro inflammatory scenario. Moreover, the fact that natural mutants of this protein elicit severe cardiovascular diseases (CVD) strongly indicates that the native folding could shift due to the mutation, yielding a structure more prone to misfold or misfunction. To understand the events that determine the failure of apoA-I structural flexibility to fulfill its protective role, we took advantage of the study of a natural variant with a deletion of the residue lysine 107 (K107del) associated with atherosclerosis. Methods: Biophysical approaches, such as electrophoresis, fluorescence and spectroscopy were used to characterize proteins structure and function, either in native conformation or under oxidation or intramolecular crosslinking. Results: K107del structure was more flexible than the protein with the native sequence (Wt) but interactions with artificial membranes were preserved. Instead, structural restrictions by intramolecular crosslinking impaired the Wt and K107del lipid solubilization function. In addition, controlled oxidation decreased the yield of the native dimer conformation for both variants. Conclusions: We conclude that even though mutations may alter protein structure and spatial arrangement, the highly flexible conformation compensates the mild shift from the native folding. Instead, post translational apoAI modifications (probably chronic and progressive) are required to raise a protein conformation with significant loss of function and increased aggregation tendency. General significance: The results learnt from this variant strength a close association between amyloidosis and atherosclerosis. |
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2021 |
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2021 |
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