X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action

Detalhes bibliográficos
Autor(a) principal: Silva, Sara T.N.
Data de Publicação: 2018
Outros Autores: Brito, José A., Arranz, Rocío, Sorzano, Carlos Óscar S., Ebel, Christine, Doutch, James, Tully, Mark D., Carazo, José María, Carrascosa, José L., Matias, Pedro M., Bandeiras, Tiago M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/85356
Resumo: RuvB-Like transcription factors function in cell cycle regulation, development and human disease, such as cancer and heart hyperplasia. The mechanisms that regulate adenosine triphosphate (ATP)-dependent activity, oligomerization and post-translational modifications in this family of enzymes are yet unknown. We present the first crystallographic structure of full-length human RuvBL2 which provides novel insights into its mechanistic action and biology. The ring-shaped hexameric RuvBL2 structure presented here resolves for the first time the mobile domain II of the human protein, which is responsible for protein-protein interactions and ATPase activity regulation. Structural analysis suggests how ATP binding may lead to domain II motion through interactions with conserved N-terminal loop histidine residues. Furthermore, a comparison between hsRuvBL1 and 2 shows differences in surface charge distribution that may account for previously described differences in regulation. Analytical ultracentrifugation and cryo electron microscopy analyses performed on hsRuvBL2 highlight an oligomer plasticity that possibly reflects different physiological conformations of the protein in the cell, as well as that single-stranded DNA (ssDNA) can promote the oligomerization of monomeric hsRuvBL2. Based on these findings, we propose a mechanism for ATP binding and domain II conformational change coupling.
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spelling X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical actionGeneralSDG 3 - Good Health and Well-beingRuvB-Like transcription factors function in cell cycle regulation, development and human disease, such as cancer and heart hyperplasia. The mechanisms that regulate adenosine triphosphate (ATP)-dependent activity, oligomerization and post-translational modifications in this family of enzymes are yet unknown. We present the first crystallographic structure of full-length human RuvBL2 which provides novel insights into its mechanistic action and biology. The ring-shaped hexameric RuvBL2 structure presented here resolves for the first time the mobile domain II of the human protein, which is responsible for protein-protein interactions and ATPase activity regulation. Structural analysis suggests how ATP binding may lead to domain II motion through interactions with conserved N-terminal loop histidine residues. Furthermore, a comparison between hsRuvBL1 and 2 shows differences in surface charge distribution that may account for previously described differences in regulation. Analytical ultracentrifugation and cryo electron microscopy analyses performed on hsRuvBL2 highlight an oligomer plasticity that possibly reflects different physiological conformations of the protein in the cell, as well as that single-stranded DNA (ssDNA) can promote the oligomerization of monomeric hsRuvBL2. Based on these findings, we propose a mechanism for ATP binding and domain II conformational change coupling.Instituto de Tecnologia Química e Biológica António Xavier (ITQB)Programme in Translational Medicine (iNOVA4Health)Molecular, Structural and Cellular Microbiology (MOSTMICRO)RUNSilva, Sara T.N.Brito, José A.Arranz, RocíoSorzano, Carlos Óscar S.Ebel, ChristineDoutch, JamesTully, Mark D.Carazo, José MaríaCarrascosa, José L.Matias, Pedro M.Bandeiras, Tiago M.2019-10-24T23:07:40Z2018-12-012018-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/85356eng2045-2322PURE: 15187659http://www.scopus.com/inward/record.url?scp=85053332823&partnerID=8YFLogxKhttps://doi.org/10.1038/s41598-018-31997-zinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:38:22Zoai:run.unl.pt:10362/85356Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:36:36.454118Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action
title X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action
spellingShingle X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action
Silva, Sara T.N.
General
SDG 3 - Good Health and Well-being
title_short X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action
title_full X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action
title_fullStr X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action
title_full_unstemmed X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action
title_sort X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action
author Silva, Sara T.N.
author_facet Silva, Sara T.N.
Brito, José A.
Arranz, Rocío
Sorzano, Carlos Óscar S.
Ebel, Christine
Doutch, James
Tully, Mark D.
Carazo, José María
Carrascosa, José L.
Matias, Pedro M.
Bandeiras, Tiago M.
author_role author
author2 Brito, José A.
Arranz, Rocío
Sorzano, Carlos Óscar S.
Ebel, Christine
Doutch, James
Tully, Mark D.
Carazo, José María
Carrascosa, José L.
Matias, Pedro M.
Bandeiras, Tiago M.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
Programme in Translational Medicine (iNOVA4Health)
Molecular, Structural and Cellular Microbiology (MOSTMICRO)
RUN
dc.contributor.author.fl_str_mv Silva, Sara T.N.
Brito, José A.
Arranz, Rocío
Sorzano, Carlos Óscar S.
Ebel, Christine
Doutch, James
Tully, Mark D.
Carazo, José María
Carrascosa, José L.
Matias, Pedro M.
Bandeiras, Tiago M.
dc.subject.por.fl_str_mv General
SDG 3 - Good Health and Well-being
topic General
SDG 3 - Good Health and Well-being
description RuvB-Like transcription factors function in cell cycle regulation, development and human disease, such as cancer and heart hyperplasia. The mechanisms that regulate adenosine triphosphate (ATP)-dependent activity, oligomerization and post-translational modifications in this family of enzymes are yet unknown. We present the first crystallographic structure of full-length human RuvBL2 which provides novel insights into its mechanistic action and biology. The ring-shaped hexameric RuvBL2 structure presented here resolves for the first time the mobile domain II of the human protein, which is responsible for protein-protein interactions and ATPase activity regulation. Structural analysis suggests how ATP binding may lead to domain II motion through interactions with conserved N-terminal loop histidine residues. Furthermore, a comparison between hsRuvBL1 and 2 shows differences in surface charge distribution that may account for previously described differences in regulation. Analytical ultracentrifugation and cryo electron microscopy analyses performed on hsRuvBL2 highlight an oligomer plasticity that possibly reflects different physiological conformations of the protein in the cell, as well as that single-stranded DNA (ssDNA) can promote the oligomerization of monomeric hsRuvBL2. Based on these findings, we propose a mechanism for ATP binding and domain II conformational change coupling.
publishDate 2018
dc.date.none.fl_str_mv 2018-12-01
2018-12-01T00:00:00Z
2019-10-24T23:07:40Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/85356
url http://hdl.handle.net/10362/85356
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2045-2322
PURE: 15187659
http://www.scopus.com/inward/record.url?scp=85053332823&partnerID=8YFLogxK
https://doi.org/10.1038/s41598-018-31997-z
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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