Discovery and investigation of natural editing function against artificial amino acids in protein translation

Autores
Völler, Jan Stefan; Dulic, Morana; Gerling Driessen, Ulla I. M.; Biava, Hernan Daniel; Baumann, Tobias; Budisa, Nediljko; Gruic Sovulj, Ita; Koksch, Beate
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fluorine being not substantially present in the chemistry of living beings is an attractive element in tailoring novel chemical, biophysical, and pharmacokinetic properties of peptides and proteins. The hallmark of ribosome-mediated artificial amino acid incorporation into peptides and proteins is a broad substrate tolerance, which is assumed to rely on the absence of evolutionary pressure for efficient editing of artificial amino acids. We used the well-characterized editing proficient isoleucyl-tRNA synthetase (IleRS) from Escherichia coli to investigate the crosstalk of aminoacylation and editing activities against fluorinated amino acids. We show that translation of trifluoroethylglycine (TfeGly) into proteins is prevented by hydrolysis of TfeGly-tRNAIle in the IleRS post-transfer editing domain. The remarkable observation is that dissociation of TfeGly-tRNAIle from IleRS is significantly slowed down. This finding is in sharp contrast to natural editing reactions by tRNA synthetases wherein fast editing rates for the noncognate substrates are essential to outcompete fast aa-tRNA dissociation rates. Using a post-transfer editing deficient mutant of IleRS (IleRSAla10), we were able to achieve ribosomal incorporation of TfeGly in vivo. Our work expands the knowledge of ribosome-mediated artificial amino acid translation with detailed analysis of natural editing function against an artificial amino acid providing an impulse for further systematic investigations and engineering of the translation and editing of unusual amino acids.
Fil: Völler, Jan Stefan. Technishe Universitat Berlin; Alemania. Freie Universität Berlin; Alemania
Fil: Dulic, Morana. University of Zagreb; Croacia
Fil: Gerling Driessen, Ulla I. M.. Freie Universität Berlin; Alemania
Fil: Biava, Hernan Daniel. Technishe Universitat Berlin; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Baumann, Tobias. Technishe Universitat Berlin; Alemania
Fil: Budisa, Nediljko. Technishe Universitat Berlin; Alemania
Fil: Gruic Sovulj, Ita. University of Zagreb; Croacia
Fil: Koksch, Beate. Freie Universität Berlin; Alemania
Materia
ARTIFICIAL AMINO ACIDS
PROTEIN TRANSLATION
NATURAL EDITING
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:11336/108134
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/108134
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Discovery and investigation of natural editing function against artificial amino acids in protein translationVöller, Jan StefanDulic, MoranaGerling Driessen, Ulla I. M.Biava, Hernan DanielBaumann, TobiasBudisa, NediljkoGruic Sovulj, ItaKoksch, BeateARTIFICIAL AMINO ACIDSPROTEIN TRANSLATIONNATURAL EDITINGhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Fluorine being not substantially present in the chemistry of living beings is an attractive element in tailoring novel chemical, biophysical, and pharmacokinetic properties of peptides and proteins. The hallmark of ribosome-mediated artificial amino acid incorporation into peptides and proteins is a broad substrate tolerance, which is assumed to rely on the absence of evolutionary pressure for efficient editing of artificial amino acids. We used the well-characterized editing proficient isoleucyl-tRNA synthetase (IleRS) from Escherichia coli to investigate the crosstalk of aminoacylation and editing activities against fluorinated amino acids. We show that translation of trifluoroethylglycine (TfeGly) into proteins is prevented by hydrolysis of TfeGly-tRNAIle in the IleRS post-transfer editing domain. The remarkable observation is that dissociation of TfeGly-tRNAIle from IleRS is significantly slowed down. This finding is in sharp contrast to natural editing reactions by tRNA synthetases wherein fast editing rates for the noncognate substrates are essential to outcompete fast aa-tRNA dissociation rates. Using a post-transfer editing deficient mutant of IleRS (IleRSAla10), we were able to achieve ribosomal incorporation of TfeGly in vivo. Our work expands the knowledge of ribosome-mediated artificial amino acid translation with detailed analysis of natural editing function against an artificial amino acid providing an impulse for further systematic investigations and engineering of the translation and editing of unusual amino acids.Fil: Völler, Jan Stefan. Technishe Universitat Berlin; Alemania. Freie Universität Berlin; AlemaniaFil: Dulic, Morana. University of Zagreb; CroaciaFil: Gerling Driessen, Ulla I. M.. Freie Universität Berlin; AlemaniaFil: Biava, Hernan Daniel. Technishe Universitat Berlin; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Baumann, Tobias. Technishe Universitat Berlin; AlemaniaFil: Budisa, Nediljko. Technishe Universitat Berlin; AlemaniaFil: Gruic Sovulj, Ita. University of Zagreb; CroaciaFil: Koksch, Beate. Freie Universität Berlin; AlemaniaAmerican Chemical Society2016-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/108134Völler, Jan Stefan; Dulic, Morana; Gerling Driessen, Ulla I. M.; Biava, Hernan Daniel; Baumann, Tobias; et al.; Discovery and investigation of natural editing function against artificial amino acids in protein translation; American Chemical Society; ACS Central Science; 3; 1; 12-2016; 73-802374-7951CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/acscentsci.6b00339info:eu-repo/semantics/altIdentifier/doi/10.1021/acscentsci.6b00339info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:46:37Zoai:ri.conicet.gov.ar:11336/108134instacron: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:34982025-09-29 10:46:38.088CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Discovery and investigation of natural editing function against artificial amino acids in protein translation
title Discovery and investigation of natural editing function against artificial amino acids in protein translation
spellingShingle Discovery and investigation of natural editing function against artificial amino acids in protein translation
Völler, Jan Stefan
ARTIFICIAL AMINO ACIDS
PROTEIN TRANSLATION
NATURAL EDITING
title_short Discovery and investigation of natural editing function against artificial amino acids in protein translation
title_full Discovery and investigation of natural editing function against artificial amino acids in protein translation
title_fullStr Discovery and investigation of natural editing function against artificial amino acids in protein translation
title_full_unstemmed Discovery and investigation of natural editing function against artificial amino acids in protein translation
title_sort Discovery and investigation of natural editing function against artificial amino acids in protein translation
dc.creator.none.fl_str_mv Völler, Jan Stefan
Dulic, Morana
Gerling Driessen, Ulla I. M.
Biava, Hernan Daniel
Baumann, Tobias
Budisa, Nediljko
Gruic Sovulj, Ita
Koksch, Beate
author Völler, Jan Stefan
author_facet Völler, Jan Stefan
Dulic, Morana
Gerling Driessen, Ulla I. M.
Biava, Hernan Daniel
Baumann, Tobias
Budisa, Nediljko
Gruic Sovulj, Ita
Koksch, Beate
author_role author
author2 Dulic, Morana
Gerling Driessen, Ulla I. M.
Biava, Hernan Daniel
Baumann, Tobias
Budisa, Nediljko
Gruic Sovulj, Ita
Koksch, Beate
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ARTIFICIAL AMINO ACIDS
PROTEIN TRANSLATION
NATURAL EDITING
topic ARTIFICIAL AMINO ACIDS
PROTEIN TRANSLATION
NATURAL EDITING
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Fluorine being not substantially present in the chemistry of living beings is an attractive element in tailoring novel chemical, biophysical, and pharmacokinetic properties of peptides and proteins. The hallmark of ribosome-mediated artificial amino acid incorporation into peptides and proteins is a broad substrate tolerance, which is assumed to rely on the absence of evolutionary pressure for efficient editing of artificial amino acids. We used the well-characterized editing proficient isoleucyl-tRNA synthetase (IleRS) from Escherichia coli to investigate the crosstalk of aminoacylation and editing activities against fluorinated amino acids. We show that translation of trifluoroethylglycine (TfeGly) into proteins is prevented by hydrolysis of TfeGly-tRNAIle in the IleRS post-transfer editing domain. The remarkable observation is that dissociation of TfeGly-tRNAIle from IleRS is significantly slowed down. This finding is in sharp contrast to natural editing reactions by tRNA synthetases wherein fast editing rates for the noncognate substrates are essential to outcompete fast aa-tRNA dissociation rates. Using a post-transfer editing deficient mutant of IleRS (IleRSAla10), we were able to achieve ribosomal incorporation of TfeGly in vivo. Our work expands the knowledge of ribosome-mediated artificial amino acid translation with detailed analysis of natural editing function against an artificial amino acid providing an impulse for further systematic investigations and engineering of the translation and editing of unusual amino acids.
Fil: Völler, Jan Stefan. Technishe Universitat Berlin; Alemania. Freie Universität Berlin; Alemania
Fil: Dulic, Morana. University of Zagreb; Croacia
Fil: Gerling Driessen, Ulla I. M.. Freie Universität Berlin; Alemania
Fil: Biava, Hernan Daniel. Technishe Universitat Berlin; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Baumann, Tobias. Technishe Universitat Berlin; Alemania
Fil: Budisa, Nediljko. Technishe Universitat Berlin; Alemania
Fil: Gruic Sovulj, Ita. University of Zagreb; Croacia
Fil: Koksch, Beate. Freie Universität Berlin; Alemania
description Fluorine being not substantially present in the chemistry of living beings is an attractive element in tailoring novel chemical, biophysical, and pharmacokinetic properties of peptides and proteins. The hallmark of ribosome-mediated artificial amino acid incorporation into peptides and proteins is a broad substrate tolerance, which is assumed to rely on the absence of evolutionary pressure for efficient editing of artificial amino acids. We used the well-characterized editing proficient isoleucyl-tRNA synthetase (IleRS) from Escherichia coli to investigate the crosstalk of aminoacylation and editing activities against fluorinated amino acids. We show that translation of trifluoroethylglycine (TfeGly) into proteins is prevented by hydrolysis of TfeGly-tRNAIle in the IleRS post-transfer editing domain. The remarkable observation is that dissociation of TfeGly-tRNAIle from IleRS is significantly slowed down. This finding is in sharp contrast to natural editing reactions by tRNA synthetases wherein fast editing rates for the noncognate substrates are essential to outcompete fast aa-tRNA dissociation rates. Using a post-transfer editing deficient mutant of IleRS (IleRSAla10), we were able to achieve ribosomal incorporation of TfeGly in vivo. Our work expands the knowledge of ribosome-mediated artificial amino acid translation with detailed analysis of natural editing function against an artificial amino acid providing an impulse for further systematic investigations and engineering of the translation and editing of unusual amino acids.
publishDate 2016
dc.date.none.fl_str_mv 2016-12
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/11336/108134
Völler, Jan Stefan; Dulic, Morana; Gerling Driessen, Ulla I. M.; Biava, Hernan Daniel; Baumann, Tobias; et al.; Discovery and investigation of natural editing function against artificial amino acids in protein translation; American Chemical Society; ACS Central Science; 3; 1; 12-2016; 73-80
2374-7951
CONICET Digital
CONICET
url http://hdl.handle.net/11336/108134
identifier_str_mv Völler, Jan Stefan; Dulic, Morana; Gerling Driessen, Ulla I. M.; Biava, Hernan Daniel; Baumann, Tobias; et al.; Discovery and investigation of natural editing function against artificial amino acids in protein translation; American Chemical Society; ACS Central Science; 3; 1; 12-2016; 73-80
2374-7951
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/acscentsci.6b00339
info:eu-repo/semantics/altIdentifier/doi/10.1021/acscentsci.6b00339
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 American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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 13.070432

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