Structural insights into TRPV2 activation by small molecules

Detalhes bibliográficos
Autor(a) principal: Pumroy, Ruth A.
Data de Publicação: 2022
Outros Autores: Protopopova, Anna D., Fricke, Tabea C., Lange, Iris U., Haug, Ferdinand M., Nguyen, Phuong T., Gallo, Pamela N., Sousa, Bárbara B., Bernardes, Gonçalo J. L., Yarov-Yarovoy, Vladimir, Leffler, Andreas, Moiseenkova-Bell, Vera Y.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/52650
Resumo: © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
id RCAP_7b515054e947199aeecd0b2dd19ea7c2
oai_identifier_str oai:repositorio.ul.pt:10451/52650
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Structural insights into TRPV2 activation by small molecules© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Transient receptor potential vanilloid 2 (TRPV2) is involved in many critical physiological and pathophysiological processes, making it a promising drug target. Here we present cryo-electron microscopy (cryo-EM) structures of rat TRPV2 in lipid nanodiscs activated by 2-aminoethoxydiphenyl borate (2-APB) and propose a TRPV2-specific 2-ABP binding site at the interface of S5 of one monomer and the S4-S5 linker of the adjacent monomer. In silico docking and electrophysiological studies confirm the key role of His521 and Arg539 in 2-APB activation of TRPV2. Additionally, electrophysiological experiments show that the combination of 2-APB and cannabidiol has a synergetic effect on TRPV2 activation, and cryo-EM structures demonstrate that both drugs were able to bind simultaneously. Together, our cryo-EM structures represent multiple functional states of the channel, providing a native picture of TRPV2 activation by small molecules and a structural framework for the development of TRPV2-specific activators.This work was supported by grants from the National Institute of Health (R01GM103899 and R01GM129357 to V.Y.M.-B.), from the Royal Society (URF\R\180019 to G.J.L.B.), from FCT Portugal (FCT Investigator, IF/00624/2015 to G.J.L.B., SFRH/BPD/143583/2019 to B.B.S.).Springer NatureRepositório da Universidade de LisboaPumroy, Ruth A.Protopopova, Anna D.Fricke, Tabea C.Lange, Iris U.Haug, Ferdinand M.Nguyen, Phuong T.Gallo, Pamela N.Sousa, Bárbara B.Bernardes, Gonçalo J. L.Yarov-Yarovoy, VladimirLeffler, AndreasMoiseenkova-Bell, Vera Y.2022-05-03T13:53:47Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/52650engNat Commun. 2022 Apr 28;13(1):233410.1038/s41467-022-30083-32041-1723info: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:RCAAP2023-11-08T16:57:59Zoai:repositorio.ul.pt:10451/52650Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:03:43.025505Repositório 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 Structural insights into TRPV2 activation by small molecules
title Structural insights into TRPV2 activation by small molecules
spellingShingle Structural insights into TRPV2 activation by small molecules
Pumroy, Ruth A.
title_short Structural insights into TRPV2 activation by small molecules
title_full Structural insights into TRPV2 activation by small molecules
title_fullStr Structural insights into TRPV2 activation by small molecules
title_full_unstemmed Structural insights into TRPV2 activation by small molecules
title_sort Structural insights into TRPV2 activation by small molecules
author Pumroy, Ruth A.
author_facet Pumroy, Ruth A.
Protopopova, Anna D.
Fricke, Tabea C.
Lange, Iris U.
Haug, Ferdinand M.
Nguyen, Phuong T.
Gallo, Pamela N.
Sousa, Bárbara B.
Bernardes, Gonçalo J. L.
Yarov-Yarovoy, Vladimir
Leffler, Andreas
Moiseenkova-Bell, Vera Y.
author_role author
author2 Protopopova, Anna D.
Fricke, Tabea C.
Lange, Iris U.
Haug, Ferdinand M.
Nguyen, Phuong T.
Gallo, Pamela N.
Sousa, Bárbara B.
Bernardes, Gonçalo J. L.
Yarov-Yarovoy, Vladimir
Leffler, Andreas
Moiseenkova-Bell, Vera Y.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Pumroy, Ruth A.
Protopopova, Anna D.
Fricke, Tabea C.
Lange, Iris U.
Haug, Ferdinand M.
Nguyen, Phuong T.
Gallo, Pamela N.
Sousa, Bárbara B.
Bernardes, Gonçalo J. L.
Yarov-Yarovoy, Vladimir
Leffler, Andreas
Moiseenkova-Bell, Vera Y.
description © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
publishDate 2022
dc.date.none.fl_str_mv 2022-05-03T13:53:47Z
2022
2022-01-01T00:00:00Z
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/10451/52650
url http://hdl.handle.net/10451/52650
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Nat Commun. 2022 Apr 28;13(1):2334
10.1038/s41467-022-30083-3
2041-1723
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.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
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
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799134587942600704