Amino acid sensor conserved from bacteria to humans

Amino acids are the building blocks of life, and they are also recognized as signals by various receptors in bacteria, archaea, and eukaryotes. Despite their common basic structure, no universal mechanism for amino acid recognition is currently known. Here, we show that a subclass of dCache_1 (doubl...

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Autores: Gumerov, Vadim M., Andrianova, E.P., Matilla, Miguel A., Page, K.M., Monteagudo-Cascales, Elizabet, Dolphin, A.C., Krell, Tino, Zhulin, Igor B.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/273112
Acceso en línea:http://hdl.handle.net/10261/273112
Access Level:acceso abierto
Palabra clave:Signal transduction
Evolution
Serine/threonine kinases
Ion channels
Gabapentin
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spelling Amino acid sensor conserved from bacteria to humansGumerov, Vadim M.Andrianova, E.P.Matilla, Miguel A.Page, K.M.Monteagudo-Cascales, ElizabetDolphin, A.C.Krell, TinoZhulin, Igor B.Signal transductionEvolutionSerine/threonine kinasesIon channelsGabapentinAmino acids are the building blocks of life, and they are also recognized as signals by various receptors in bacteria, archaea, and eukaryotes. Despite their common basic structure, no universal mechanism for amino acid recognition is currently known. Here, we show that a subclass of dCache_1 (double domain found in calcium channels and chemotaxis receptors, family 1), a ubiquitous extracellular sensory domain, contains a simple motif, which recognizes the amino and carboxyl groups of amino acid ligands. We found this motif throughout the Tree of Life. In bacteria and archaea, this motif exclusively binds amino acids, including γ-aminobutyric acid (GABA), and it is present in all major receptor types. In humans, this motif is found in α2δ-subunits of voltage-gated calcium channels that are implicated in neuropathic pain and neurodevelopmental disorders and in a recently characterized CACHD1 protein. Our findings suggest that GABA-derived drugs bind to the same motif in human α2δ-subunits that binds natural GABA ligands in bacterial chemoreceptors. The exact location on the target protein and the mechanism of binding may enable future improvements of drugs targeting pain and neurobiological disorders.This study was supported by Spanish Ministry of Science and Innovation/Agencia Estatal de Investigacion Grants PID2019-103972GA-100 (to M.A.M.) and PID2020-112612GB-100 (to T.K.); Wellcome Trust Grant 206279\Z\17\Z (to A.C.D.); Junta de Andalucia Grant P18-FR-1621 (to T.K.); and NIH Grant 1R35GM131760 (to I.B.Z.). K.M.P. and A.C.D. thank Wendy S. Pratt for molecular biology support.Peer reviewedNational Academy of Sciences (U.S.)European CommissionMinisterio de Ciencia e Innovación (España)Junta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/273112reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-103972GA-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-112612GB-I00http://dx.doi.org/10.1073/pnas.2110415119Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2731122026-05-22T06:33:51Z
dc.title.none.fl_str_mv Amino acid sensor conserved from bacteria to humans
title Amino acid sensor conserved from bacteria to humans
spellingShingle Amino acid sensor conserved from bacteria to humans
Gumerov, Vadim M.
Signal transduction
Evolution
Serine/threonine kinases
Ion channels
Gabapentin
title_short Amino acid sensor conserved from bacteria to humans
title_full Amino acid sensor conserved from bacteria to humans
title_fullStr Amino acid sensor conserved from bacteria to humans
title_full_unstemmed Amino acid sensor conserved from bacteria to humans
title_sort Amino acid sensor conserved from bacteria to humans
dc.creator.none.fl_str_mv Gumerov, Vadim M.
Andrianova, E.P.
Matilla, Miguel A.
Page, K.M.
Monteagudo-Cascales, Elizabet
Dolphin, A.C.
Krell, Tino
Zhulin, Igor B.
author Gumerov, Vadim M.
author_facet Gumerov, Vadim M.
Andrianova, E.P.
Matilla, Miguel A.
Page, K.M.
Monteagudo-Cascales, Elizabet
Dolphin, A.C.
Krell, Tino
Zhulin, Igor B.
author_role author
author2 Andrianova, E.P.
Matilla, Miguel A.
Page, K.M.
Monteagudo-Cascales, Elizabet
Dolphin, A.C.
Krell, Tino
Zhulin, Igor B.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Ministerio de Ciencia e Innovación (España)
Junta de Andalucía
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Signal transduction
Evolution
Serine/threonine kinases
Ion channels
Gabapentin
topic Signal transduction
Evolution
Serine/threonine kinases
Ion channels
Gabapentin
description Amino acids are the building blocks of life, and they are also recognized as signals by various receptors in bacteria, archaea, and eukaryotes. Despite their common basic structure, no universal mechanism for amino acid recognition is currently known. Here, we show that a subclass of dCache_1 (double domain found in calcium channels and chemotaxis receptors, family 1), a ubiquitous extracellular sensory domain, contains a simple motif, which recognizes the amino and carboxyl groups of amino acid ligands. We found this motif throughout the Tree of Life. In bacteria and archaea, this motif exclusively binds amino acids, including γ-aminobutyric acid (GABA), and it is present in all major receptor types. In humans, this motif is found in α2δ-subunits of voltage-gated calcium channels that are implicated in neuropathic pain and neurodevelopmental disorders and in a recently characterized CACHD1 protein. Our findings suggest that GABA-derived drugs bind to the same motif in human α2δ-subunits that binds natural GABA ligands in bacterial chemoreceptors. The exact location on the target protein and the mechanism of binding may enable future improvements of drugs targeting pain and neurobiological disorders.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/273112
url http://hdl.handle.net/10261/273112
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-103972GA-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-112612GB-I00
http://dx.doi.org/10.1073/pnas.2110415119
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv National Academy of Sciences (U.S.)
publisher.none.fl_str_mv National Academy of Sciences (U.S.)
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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