The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformation

Autores
Lisa, María Natalia; Wagner, Tristan; Alexandre, Matthieu; Barilone, Nathalie; Raynal, Bertrand; Alzari, Pedro M.; Bellinzoni, Marco
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Eukaryotic-like Ser/Thr protein kinases (ePKs) have been identified in many bacterial species, where they are known to mediate signalling mechanisms that share several features with their eukaryotic counterparts. In Mycobacterium tuberculosis, PknI is one of the 11 predicted ePKs and it has been related to bacterial virulence. In order to better understand the molecular basis of its role in mycobacterial signalling, we solved the crystal structure of the PknI cytoplasmic domain. We found that even though PknI possesses most conserved elements characteristic of Hanks-type kinases, it is degraded in several motifs that are essential for the ePKs catalytic activity. Most notably, PknI presents a remarkably short activation segment lacking a peptide–substrate binding site. Consistent with this observation and similar to earlier findings for eukaryotic pseudokinases, no kinase activity was detected for the catalytic domain of PknI, against different substrates and in various experimental conditions. Based on these results, we conclude that PknI may rely on unconventional mechanism(s) for kinase activity and/or it could play alternative role(s) in mycobacterial signalling. Database: Atomic coordinates and structure factors for the catalytic domain of M. tuberculosis PknI are in the Protein Data Bank under the accession codes 5M06 (wild-type PknI + ADP), 5M07 (PknI_C20A), 5M08 (PknI_C20A_R136A) and 5M09 (PknI_C20A_R136N).
Fil: Lisa, María Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universite de Paris V; Francia. Instituto Pasteur; Francia
Fil: Wagner, Tristan. Instituto Pasteur; Francia. Universite de Paris V; Francia
Fil: Alexandre, Matthieu. Instituto Pasteur; Francia. Universite de Paris V; Francia
Fil: Barilone, Nathalie. Instituto Pasteur; Francia. Universite de Paris V; Francia
Fil: Raynal, Bertrand. Instituto Pasteur; Francia. Universite de Paris V; Francia
Fil: Alzari, Pedro M.. Instituto Pasteur; Francia. Universite de Paris V; Francia
Fil: Bellinzoni, Marco. Instituto Pasteur; Francia. Universite de Paris V; Francia
Materia
ACTIVATION SEGMENT
SER/THR KINASE
SIGNAL TRANSDUCTION
X-RAY CRYSTALLOGRAPHY
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:11336/66031
Acceder
id CONICETDig_520bc277d2a357cc6af3a1ace516300f
oai_identifier_str oai:ri.conicet.gov.ar:11336/66031
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformationLisa, María NataliaWagner, TristanAlexandre, MatthieuBarilone, NathalieRaynal, BertrandAlzari, Pedro M.Bellinzoni, MarcoACTIVATION SEGMENTSER/THR KINASESIGNAL TRANSDUCTIONX-RAY CRYSTALLOGRAPHYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Eukaryotic-like Ser/Thr protein kinases (ePKs) have been identified in many bacterial species, where they are known to mediate signalling mechanisms that share several features with their eukaryotic counterparts. In Mycobacterium tuberculosis, PknI is one of the 11 predicted ePKs and it has been related to bacterial virulence. In order to better understand the molecular basis of its role in mycobacterial signalling, we solved the crystal structure of the PknI cytoplasmic domain. We found that even though PknI possesses most conserved elements characteristic of Hanks-type kinases, it is degraded in several motifs that are essential for the ePKs catalytic activity. Most notably, PknI presents a remarkably short activation segment lacking a peptide–substrate binding site. Consistent with this observation and similar to earlier findings for eukaryotic pseudokinases, no kinase activity was detected for the catalytic domain of PknI, against different substrates and in various experimental conditions. Based on these results, we conclude that PknI may rely on unconventional mechanism(s) for kinase activity and/or it could play alternative role(s) in mycobacterial signalling. Database: Atomic coordinates and structure factors for the catalytic domain of M. tuberculosis PknI are in the Protein Data Bank under the accession codes 5M06 (wild-type PknI + ADP), 5M07 (PknI_C20A), 5M08 (PknI_C20A_R136A) and 5M09 (PknI_C20A_R136N).Fil: Lisa, María Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universite de Paris V; Francia. Instituto Pasteur; FranciaFil: Wagner, Tristan. Instituto Pasteur; Francia. Universite de Paris V; FranciaFil: Alexandre, Matthieu. Instituto Pasteur; Francia. Universite de Paris V; FranciaFil: Barilone, Nathalie. Instituto Pasteur; Francia. Universite de Paris V; FranciaFil: Raynal, Bertrand. Instituto Pasteur; Francia. Universite de Paris V; FranciaFil: Alzari, Pedro M.. Instituto Pasteur; Francia. Universite de Paris V; FranciaFil: Bellinzoni, Marco. Instituto Pasteur; Francia. Universite de Paris V; FranciaWiley Blackwell Publishing, Inc2017-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/66031Lisa, María Natalia; Wagner, Tristan; Alexandre, Matthieu; Barilone, Nathalie; Raynal, Bertrand; et al.; The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformation; Wiley Blackwell Publishing, Inc; Febs Journal; 284; 4; 2-2017; 602-6141742-464XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/febs.14003/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1111/febs.14003info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:16:12Zoai:ri.conicet.gov.ar:11336/66031instacron: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:34982025-10-22 11:16:12.716CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformation
title The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformation
spellingShingle The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformation
Lisa, María Natalia
ACTIVATION SEGMENT
SER/THR KINASE
SIGNAL TRANSDUCTION
X-RAY CRYSTALLOGRAPHY
title_short The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformation
title_full The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformation
title_fullStr The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformation
title_full_unstemmed The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformation
title_sort The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformation
dc.creator.none.fl_str_mv Lisa, María Natalia
Wagner, Tristan
Alexandre, Matthieu
Barilone, Nathalie
Raynal, Bertrand
Alzari, Pedro M.
Bellinzoni, Marco
author Lisa, María Natalia
author_facet Lisa, María Natalia
Wagner, Tristan
Alexandre, Matthieu
Barilone, Nathalie
Raynal, Bertrand
Alzari, Pedro M.
Bellinzoni, Marco
author_role author
author2 Wagner, Tristan
Alexandre, Matthieu
Barilone, Nathalie
Raynal, Bertrand
Alzari, Pedro M.
Bellinzoni, Marco
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ACTIVATION SEGMENT
SER/THR KINASE
SIGNAL TRANSDUCTION
X-RAY CRYSTALLOGRAPHY
topic ACTIVATION SEGMENT
SER/THR KINASE
SIGNAL TRANSDUCTION
X-RAY CRYSTALLOGRAPHY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Eukaryotic-like Ser/Thr protein kinases (ePKs) have been identified in many bacterial species, where they are known to mediate signalling mechanisms that share several features with their eukaryotic counterparts. In Mycobacterium tuberculosis, PknI is one of the 11 predicted ePKs and it has been related to bacterial virulence. In order to better understand the molecular basis of its role in mycobacterial signalling, we solved the crystal structure of the PknI cytoplasmic domain. We found that even though PknI possesses most conserved elements characteristic of Hanks-type kinases, it is degraded in several motifs that are essential for the ePKs catalytic activity. Most notably, PknI presents a remarkably short activation segment lacking a peptide–substrate binding site. Consistent with this observation and similar to earlier findings for eukaryotic pseudokinases, no kinase activity was detected for the catalytic domain of PknI, against different substrates and in various experimental conditions. Based on these results, we conclude that PknI may rely on unconventional mechanism(s) for kinase activity and/or it could play alternative role(s) in mycobacterial signalling. Database: Atomic coordinates and structure factors for the catalytic domain of M. tuberculosis PknI are in the Protein Data Bank under the accession codes 5M06 (wild-type PknI + ADP), 5M07 (PknI_C20A), 5M08 (PknI_C20A_R136A) and 5M09 (PknI_C20A_R136N).
Fil: Lisa, María Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universite de Paris V; Francia. Instituto Pasteur; Francia
Fil: Wagner, Tristan. Instituto Pasteur; Francia. Universite de Paris V; Francia
Fil: Alexandre, Matthieu. Instituto Pasteur; Francia. Universite de Paris V; Francia
Fil: Barilone, Nathalie. Instituto Pasteur; Francia. Universite de Paris V; Francia
Fil: Raynal, Bertrand. Instituto Pasteur; Francia. Universite de Paris V; Francia
Fil: Alzari, Pedro M.. Instituto Pasteur; Francia. Universite de Paris V; Francia
Fil: Bellinzoni, Marco. Instituto Pasteur; Francia. Universite de Paris V; Francia
description Eukaryotic-like Ser/Thr protein kinases (ePKs) have been identified in many bacterial species, where they are known to mediate signalling mechanisms that share several features with their eukaryotic counterparts. In Mycobacterium tuberculosis, PknI is one of the 11 predicted ePKs and it has been related to bacterial virulence. In order to better understand the molecular basis of its role in mycobacterial signalling, we solved the crystal structure of the PknI cytoplasmic domain. We found that even though PknI possesses most conserved elements characteristic of Hanks-type kinases, it is degraded in several motifs that are essential for the ePKs catalytic activity. Most notably, PknI presents a remarkably short activation segment lacking a peptide–substrate binding site. Consistent with this observation and similar to earlier findings for eukaryotic pseudokinases, no kinase activity was detected for the catalytic domain of PknI, against different substrates and in various experimental conditions. Based on these results, we conclude that PknI may rely on unconventional mechanism(s) for kinase activity and/or it could play alternative role(s) in mycobacterial signalling. Database: Atomic coordinates and structure factors for the catalytic domain of M. tuberculosis PknI are in the Protein Data Bank under the accession codes 5M06 (wild-type PknI + ADP), 5M07 (PknI_C20A), 5M08 (PknI_C20A_R136A) and 5M09 (PknI_C20A_R136N).
publishDate 2017
dc.date.none.fl_str_mv 2017-02
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/11336/66031
Lisa, María Natalia; Wagner, Tristan; Alexandre, Matthieu; Barilone, Nathalie; Raynal, Bertrand; et al.; The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformation; Wiley Blackwell Publishing, Inc; Febs Journal; 284; 4; 2-2017; 602-614
1742-464X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/66031
identifier_str_mv Lisa, María Natalia; Wagner, Tristan; Alexandre, Matthieu; Barilone, Nathalie; Raynal, Bertrand; et al.; The crystal structure of PknI from Mycobacterium tuberculosis shows an inactive, pseudokinase-like conformation; Wiley Blackwell Publishing, Inc; Febs Journal; 284; 4; 2-2017; 602-614
1742-464X
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://onlinelibrary.wiley.com/doi/10.1111/febs.14003/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1111/febs.14003
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 Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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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