Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains

Autores
Azizyan, Rafayel A.; Garro, Adriana; Radkova, Zinaida; Anikeenko, Alexey; Bakulina, Anastasia; Dumas, Christian; Kajava, Andrey V.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In many disease-related and functional amyloids, the amyloid-forming regions of proteins are flanked by globular domains. When located in close vicinity of the amyloid regions along the chain, the globular domains can prevent the formation of amyloids because of the steric repulsion. Experimental tests of this effect are few in number and non-systematic, and their interpretation is hampered by polymorphism of amyloid structures. In this situation, modeling approaches that use such a clear-cut criterion as the steric tension can give us highly trustworthy results. In this work, we evaluated this steric effect by using molecular modeling and dynamics. As an example, we tested hybrid proteins containing an amyloid-forming fragment of Aβ peptide (17–42) linked to one or two globular domains of GFP. Searching for the shortest possible linker, we constructed models with pseudo-helical arrangements of the densely packed GFPs around the Aβ amyloid core. The molecular modeling showed that linkers of 7 and more residues allow fibrillogenesis of the Aβ-peptide flanked by GFP on one side and 18 and more residues when Aβ-peptide is flanked by GFPs on both sides. Furthermore, we were able to establish a more general relationship between the size of the globular domains and the length of the linkers by using analytical expressions and rigid body simulations. Our results will find use in planning and interpretation of experiments, improvement of the prediction of amyloidogenic regions in proteins, and design of new functional amyloids carrying globular domains.
Fil: Azizyan, Rafayel A.. Université Montpellier. Institut de Biologie Computationnelle; Francia. Université Montpellier. Centre de Recherche en Biologie cellulaire de Montpellierf; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Garro, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; Argentina
Fil: Radkova, Zinaida. Novosibirsk State University; Rusia
Fil: Anikeenko, Alexey. Novosibirsk State University; Rusia
Fil: Bakulina, Anastasia. Novosibirsk State University; Rusia
Fil: Dumas, Christian. Centre National de la Recherche Scientifique; Francia. Centre de Biochimie Structurale; Francia
Fil: Kajava, Andrey V.. Centre National de la Recherche Scientifique; Francia. Université Montpellier. Centre de Recherche en Biologie cellulaire de Montpellierf; Francia. Université Montpellier. Institut de Biologie Computationnelle; Francia
Materia
AGGREGATION
AMYLOIDS
FIBRILLOGENESIS
PROTEIN STRUCTURE
RIGID BODY SIMULATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/88980
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/88980
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular DomainsAzizyan, Rafayel A.Garro, AdrianaRadkova, ZinaidaAnikeenko, AlexeyBakulina, AnastasiaDumas, ChristianKajava, Andrey V.AGGREGATIONAMYLOIDSFIBRILLOGENESISPROTEIN STRUCTURERIGID BODY SIMULATIONhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1In many disease-related and functional amyloids, the amyloid-forming regions of proteins are flanked by globular domains. When located in close vicinity of the amyloid regions along the chain, the globular domains can prevent the formation of amyloids because of the steric repulsion. Experimental tests of this effect are few in number and non-systematic, and their interpretation is hampered by polymorphism of amyloid structures. In this situation, modeling approaches that use such a clear-cut criterion as the steric tension can give us highly trustworthy results. In this work, we evaluated this steric effect by using molecular modeling and dynamics. As an example, we tested hybrid proteins containing an amyloid-forming fragment of Aβ peptide (17–42) linked to one or two globular domains of GFP. Searching for the shortest possible linker, we constructed models with pseudo-helical arrangements of the densely packed GFPs around the Aβ amyloid core. The molecular modeling showed that linkers of 7 and more residues allow fibrillogenesis of the Aβ-peptide flanked by GFP on one side and 18 and more residues when Aβ-peptide is flanked by GFPs on both sides. Furthermore, we were able to establish a more general relationship between the size of the globular domains and the length of the linkers by using analytical expressions and rigid body simulations. Our results will find use in planning and interpretation of experiments, improvement of the prediction of amyloidogenic regions in proteins, and design of new functional amyloids carrying globular domains.Fil: Azizyan, Rafayel A.. Université Montpellier. Institut de Biologie Computationnelle; Francia. Université Montpellier. Centre de Recherche en Biologie cellulaire de Montpellierf; Francia. Centre National de la Recherche Scientifique; FranciaFil: Garro, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; ArgentinaFil: Radkova, Zinaida. Novosibirsk State University; RusiaFil: Anikeenko, Alexey. Novosibirsk State University; RusiaFil: Bakulina, Anastasia. Novosibirsk State University; RusiaFil: Dumas, Christian. Centre National de la Recherche Scientifique; Francia. Centre de Biochimie Structurale; FranciaFil: Kajava, Andrey V.. Centre National de la Recherche Scientifique; Francia. Université Montpellier. Centre de Recherche en Biologie cellulaire de Montpellierf; Francia. Université Montpellier. Institut de Biologie Computationnelle; FranciaAcademic Press Ltd - Elsevier Science Ltd2018-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/88980Azizyan, Rafayel A.; Garro, Adriana; Radkova, Zinaida; Anikeenko, Alexey; Bakulina, Anastasia; et al.; Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains; Academic Press Ltd - Elsevier Science Ltd; Journal Of Molecular Biology; 430; 20; 10-2018; 3835-38460022-2836CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jmb.2018.05.038info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022283618305333info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:45Zoai:ri.conicet.gov.ar:11336/88980instacron: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:34982025-09-03 09:55:46.188CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains
title Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains
spellingShingle Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains
Azizyan, Rafayel A.
AGGREGATION
AMYLOIDS
FIBRILLOGENESIS
PROTEIN STRUCTURE
RIGID BODY SIMULATION
title_short Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains
title_full Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains
title_fullStr Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains
title_full_unstemmed Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains
title_sort Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains
dc.creator.none.fl_str_mv Azizyan, Rafayel A.
Garro, Adriana
Radkova, Zinaida
Anikeenko, Alexey
Bakulina, Anastasia
Dumas, Christian
Kajava, Andrey V.
author Azizyan, Rafayel A.
author_facet Azizyan, Rafayel A.
Garro, Adriana
Radkova, Zinaida
Anikeenko, Alexey
Bakulina, Anastasia
Dumas, Christian
Kajava, Andrey V.
author_role author
author2 Garro, Adriana
Radkova, Zinaida
Anikeenko, Alexey
Bakulina, Anastasia
Dumas, Christian
Kajava, Andrey V.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv AGGREGATION
AMYLOIDS
FIBRILLOGENESIS
PROTEIN STRUCTURE
RIGID BODY SIMULATION
topic AGGREGATION
AMYLOIDS
FIBRILLOGENESIS
PROTEIN STRUCTURE
RIGID BODY SIMULATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In many disease-related and functional amyloids, the amyloid-forming regions of proteins are flanked by globular domains. When located in close vicinity of the amyloid regions along the chain, the globular domains can prevent the formation of amyloids because of the steric repulsion. Experimental tests of this effect are few in number and non-systematic, and their interpretation is hampered by polymorphism of amyloid structures. In this situation, modeling approaches that use such a clear-cut criterion as the steric tension can give us highly trustworthy results. In this work, we evaluated this steric effect by using molecular modeling and dynamics. As an example, we tested hybrid proteins containing an amyloid-forming fragment of Aβ peptide (17–42) linked to one or two globular domains of GFP. Searching for the shortest possible linker, we constructed models with pseudo-helical arrangements of the densely packed GFPs around the Aβ amyloid core. The molecular modeling showed that linkers of 7 and more residues allow fibrillogenesis of the Aβ-peptide flanked by GFP on one side and 18 and more residues when Aβ-peptide is flanked by GFPs on both sides. Furthermore, we were able to establish a more general relationship between the size of the globular domains and the length of the linkers by using analytical expressions and rigid body simulations. Our results will find use in planning and interpretation of experiments, improvement of the prediction of amyloidogenic regions in proteins, and design of new functional amyloids carrying globular domains.
Fil: Azizyan, Rafayel A.. Université Montpellier. Institut de Biologie Computationnelle; Francia. Université Montpellier. Centre de Recherche en Biologie cellulaire de Montpellierf; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Garro, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; Argentina
Fil: Radkova, Zinaida. Novosibirsk State University; Rusia
Fil: Anikeenko, Alexey. Novosibirsk State University; Rusia
Fil: Bakulina, Anastasia. Novosibirsk State University; Rusia
Fil: Dumas, Christian. Centre National de la Recherche Scientifique; Francia. Centre de Biochimie Structurale; Francia
Fil: Kajava, Andrey V.. Centre National de la Recherche Scientifique; Francia. Université Montpellier. Centre de Recherche en Biologie cellulaire de Montpellierf; Francia. Université Montpellier. Institut de Biologie Computationnelle; Francia
description In many disease-related and functional amyloids, the amyloid-forming regions of proteins are flanked by globular domains. When located in close vicinity of the amyloid regions along the chain, the globular domains can prevent the formation of amyloids because of the steric repulsion. Experimental tests of this effect are few in number and non-systematic, and their interpretation is hampered by polymorphism of amyloid structures. In this situation, modeling approaches that use such a clear-cut criterion as the steric tension can give us highly trustworthy results. In this work, we evaluated this steric effect by using molecular modeling and dynamics. As an example, we tested hybrid proteins containing an amyloid-forming fragment of Aβ peptide (17–42) linked to one or two globular domains of GFP. Searching for the shortest possible linker, we constructed models with pseudo-helical arrangements of the densely packed GFPs around the Aβ amyloid core. The molecular modeling showed that linkers of 7 and more residues allow fibrillogenesis of the Aβ-peptide flanked by GFP on one side and 18 and more residues when Aβ-peptide is flanked by GFPs on both sides. Furthermore, we were able to establish a more general relationship between the size of the globular domains and the length of the linkers by using analytical expressions and rigid body simulations. Our results will find use in planning and interpretation of experiments, improvement of the prediction of amyloidogenic regions in proteins, and design of new functional amyloids carrying globular domains.
publishDate 2018
dc.date.none.fl_str_mv 2018-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/88980
Azizyan, Rafayel A.; Garro, Adriana; Radkova, Zinaida; Anikeenko, Alexey; Bakulina, Anastasia; et al.; Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains; Academic Press Ltd - Elsevier Science Ltd; Journal Of Molecular Biology; 430; 20; 10-2018; 3835-3846
0022-2836
CONICET Digital
CONICET
url http://hdl.handle.net/11336/88980
identifier_str_mv Azizyan, Rafayel A.; Garro, Adriana; Radkova, Zinaida; Anikeenko, Alexey; Bakulina, Anastasia; et al.; Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains; Academic Press Ltd - Elsevier Science Ltd; Journal Of Molecular Biology; 430; 20; 10-2018; 3835-3846
0022-2836
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jmb.2018.05.038
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022283618305333
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Ltd - Elsevier Science Ltd
publisher.none.fl_str_mv Academic Press Ltd - Elsevier Science Ltd
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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