Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regions

Autores
Racigh, Vanesa Elizabeth; Rodriguez Sawicki, Luciana; Bravo, Facundo Nicolás Eric; Fornasari, Maria Silvina
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Human small Heat Shock Protein 1 (HSPB1) belongs to the Small Heat Shock Protein (sHSP) superfamily, a group of ATP-independent molecular chaperones essential for cellular stress responses and protein quality control. These proteins share a conserved domain organization, with a structured Alpha-Crystallin domain (ACD) flanked by disordered N-terminal and C-terminal regions (NTR and CTR). While the prevailing evolutionary hypothesis for the sHSP family suggests that the disordered regions evolved independently and at a faster rate than the ACD, this study provides, for the first time, evidence of coevolution between these regions in human HSPB1, introducing new insights into the evolutionary mechanisms that sustain critical regulatory interactions. By integrating evolutionary and structural approaches, we estimated evolutionary rates per region and position, analyzed the composition of key interacting motifs, and employed structural modeling with AlphaFold 2 to assess the prevalence of these interactions. Our findings reveal that while the disordered regions globally evolve faster than the ACD, specific motifs involved in regulatory interactions exhibit lower-than-average evolutionary rates, reflecting evolutionary constraints imposed by their functional importance. This coevolutionary mechanism may also extend to other small Heat Shock Proteins featuring interacting motifs in the NTR, CTR, or both, offering a new perspective for studying their molecular evolution. Furthermore, the analysis presented in this work could be applied to assess coevolution in other proteins with intrinsically disordered regions.
Fil: Racigh, Vanesa Elizabeth. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rodriguez Sawicki, Luciana. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bravo, Facundo Nicolás Eric. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Small Heat Shock Protein 1
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:11336/265867
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regionsRacigh, Vanesa ElizabethRodriguez Sawicki, LucianaBravo, Facundo Nicolás EricFornasari, Maria SilvinaSmall Heat Shock Protein 1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Human small Heat Shock Protein 1 (HSPB1) belongs to the Small Heat Shock Protein (sHSP) superfamily, a group of ATP-independent molecular chaperones essential for cellular stress responses and protein quality control. These proteins share a conserved domain organization, with a structured Alpha-Crystallin domain (ACD) flanked by disordered N-terminal and C-terminal regions (NTR and CTR). While the prevailing evolutionary hypothesis for the sHSP family suggests that the disordered regions evolved independently and at a faster rate than the ACD, this study provides, for the first time, evidence of coevolution between these regions in human HSPB1, introducing new insights into the evolutionary mechanisms that sustain critical regulatory interactions. By integrating evolutionary and structural approaches, we estimated evolutionary rates per region and position, analyzed the composition of key interacting motifs, and employed structural modeling with AlphaFold 2 to assess the prevalence of these interactions. Our findings reveal that while the disordered regions globally evolve faster than the ACD, specific motifs involved in regulatory interactions exhibit lower-than-average evolutionary rates, reflecting evolutionary constraints imposed by their functional importance. This coevolutionary mechanism may also extend to other small Heat Shock Proteins featuring interacting motifs in the NTR, CTR, or both, offering a new perspective for studying their molecular evolution. Furthermore, the analysis presented in this work could be applied to assess coevolution in other proteins with intrinsically disordered regions.Fil: Racigh, Vanesa Elizabeth. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodriguez Sawicki, Luciana. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bravo, Facundo Nicolás Eric. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaPublic Library of Science2025-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/265867Racigh, Vanesa Elizabeth; Rodriguez Sawicki, Luciana; Bravo, Facundo Nicolás Eric; Fornasari, Maria Silvina; Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regions; Public Library of Science; Plos One; 20; 5; 5-2025; 1-181932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://dx.plos.org/10.1371/journal.pone.0321163info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0321163info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:25Zoai:ri.conicet.gov.ar:11336/265867instacron: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 10:08:25.908CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regions
title Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regions
spellingShingle Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regions
Racigh, Vanesa Elizabeth
Small Heat Shock Protein 1
title_short Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regions
title_full Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regions
title_fullStr Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regions
title_full_unstemmed Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regions
title_sort Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regions
dc.creator.none.fl_str_mv Racigh, Vanesa Elizabeth
Rodriguez Sawicki, Luciana
Bravo, Facundo Nicolás Eric
Fornasari, Maria Silvina
author Racigh, Vanesa Elizabeth
author_facet Racigh, Vanesa Elizabeth
Rodriguez Sawicki, Luciana
Bravo, Facundo Nicolás Eric
Fornasari, Maria Silvina
author_role author
author2 Rodriguez Sawicki, Luciana
Bravo, Facundo Nicolás Eric
Fornasari, Maria Silvina
author2_role author
author
author
dc.subject.none.fl_str_mv Small Heat Shock Protein 1
topic Small Heat Shock Protein 1
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 small Heat Shock Protein 1 (HSPB1) belongs to the Small Heat Shock Protein (sHSP) superfamily, a group of ATP-independent molecular chaperones essential for cellular stress responses and protein quality control. These proteins share a conserved domain organization, with a structured Alpha-Crystallin domain (ACD) flanked by disordered N-terminal and C-terminal regions (NTR and CTR). While the prevailing evolutionary hypothesis for the sHSP family suggests that the disordered regions evolved independently and at a faster rate than the ACD, this study provides, for the first time, evidence of coevolution between these regions in human HSPB1, introducing new insights into the evolutionary mechanisms that sustain critical regulatory interactions. By integrating evolutionary and structural approaches, we estimated evolutionary rates per region and position, analyzed the composition of key interacting motifs, and employed structural modeling with AlphaFold 2 to assess the prevalence of these interactions. Our findings reveal that while the disordered regions globally evolve faster than the ACD, specific motifs involved in regulatory interactions exhibit lower-than-average evolutionary rates, reflecting evolutionary constraints imposed by their functional importance. This coevolutionary mechanism may also extend to other small Heat Shock Proteins featuring interacting motifs in the NTR, CTR, or both, offering a new perspective for studying their molecular evolution. Furthermore, the analysis presented in this work could be applied to assess coevolution in other proteins with intrinsically disordered regions.
Fil: Racigh, Vanesa Elizabeth. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rodriguez Sawicki, Luciana. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bravo, Facundo Nicolás Eric. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Human small Heat Shock Protein 1 (HSPB1) belongs to the Small Heat Shock Protein (sHSP) superfamily, a group of ATP-independent molecular chaperones essential for cellular stress responses and protein quality control. These proteins share a conserved domain organization, with a structured Alpha-Crystallin domain (ACD) flanked by disordered N-terminal and C-terminal regions (NTR and CTR). While the prevailing evolutionary hypothesis for the sHSP family suggests that the disordered regions evolved independently and at a faster rate than the ACD, this study provides, for the first time, evidence of coevolution between these regions in human HSPB1, introducing new insights into the evolutionary mechanisms that sustain critical regulatory interactions. By integrating evolutionary and structural approaches, we estimated evolutionary rates per region and position, analyzed the composition of key interacting motifs, and employed structural modeling with AlphaFold 2 to assess the prevalence of these interactions. Our findings reveal that while the disordered regions globally evolve faster than the ACD, specific motifs involved in regulatory interactions exhibit lower-than-average evolutionary rates, reflecting evolutionary constraints imposed by their functional importance. This coevolutionary mechanism may also extend to other small Heat Shock Proteins featuring interacting motifs in the NTR, CTR, or both, offering a new perspective for studying their molecular evolution. Furthermore, the analysis presented in this work could be applied to assess coevolution in other proteins with intrinsically disordered regions.
publishDate 2025
dc.date.none.fl_str_mv 2025-05
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/11336/265867
Racigh, Vanesa Elizabeth; Rodriguez Sawicki, Luciana; Bravo, Facundo Nicolás Eric; Fornasari, Maria Silvina; Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regions; Public Library of Science; Plos One; 20; 5; 5-2025; 1-18
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/265867
identifier_str_mv Racigh, Vanesa Elizabeth; Rodriguez Sawicki, Luciana; Bravo, Facundo Nicolás Eric; Fornasari, Maria Silvina; Coevolution in human small Heat Shock Protein 1 is promoted by interactions between the Alpha-Crystallin domain and the disordered regions; Public Library of Science; Plos One; 20; 5; 5-2025; 1-18
1932-6203
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://dx.plos.org/10.1371/journal.pone.0321163
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0321163
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
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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score 13.13397

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