Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL

Autores
Miguel, Virginia; Correa, Elisa María Eugenia; de Tullio, Luisina; Barra, Jose Luis; Argaraña, Carlos Enrique; Villarreal, Marcos Ariel
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mismatch Repair System corrects mutations arising from DNA replication that escape from DNA polymerase proofreadingactivity. This system consists of three main proteins, MutS-L-H, responsible for lesion recognition and repair. MutL is amember of GHKL ATPase family and its ATPase cycle has been proposed to modulate MutL activity during the repairprocess. Pseudomonas aeruginosa MutL (PaMutL) contains an N-terminal (NTD) ATPase domain connected by a linker to a C-terminal (CTD) dimerization domain that possesses metal ion-dependent endonuclease activity. With the aim to identifycharacteristics that allow the PaMutL NTD allosteric control of CTD endonuclease activity, we used an in silico andexperimental approach to determine the interaction surfaces of P. aeruginosa NTD (PaNTD), and compared it with the wellcharacterized Escherichia coli MutL NTD (EcNTD). Molecular dynamics simulations of PaNTD and EcNTD bound to or free ofadenosine nucleotides showed that a significant difference exists between the behavior of the EcNTD and PaNTDdimerization interface, particularly in the ATP lid. Structure based simulations of MutL homologues with endonucleaseactivity were performed that allowed an insight of the dimerization interface behavior in this family of proteins. Ourexperimental results show that, unlike EcNTD, PaNTD is dimeric in presence of ADP. Simulations in mixed solvent allowed usto identify the PaNTD putative DNA binding patch and a putative interaction patch located opposite to the dimerizationface. Structure based simulations of PaNTD dimer in presence of ADP or ATP suggest that nucleotide binding coulddifferentially modulate PaNTD protein-protein interactions. Far western assays performed in presence of ADP or ATP are inagreement with our in silico analysis.
Fil: Miguel, Virginia. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p);
Fil: Correa, Elisa María Eugenia. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p); Argentina
Fil: de Tullio, Luisina. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p); Argentina
Fil: Barra, Jose Luis. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p); Argentina
Fil: Argaraña, Carlos Enrique. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p);
Fil: Villarreal, Marcos Ariel. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Instituto de Investigaciones En Fisico- Quimica de Cordoba; Argentina
Materia
P. aeruginosa
MutL
protein-protein interaction
Bioinformatic
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/549
Acceder
id CONICETDig_c8c101131cdc0607253c7c9d6312459b
oai_identifier_str oai:ri.conicet.gov.ar:11336/549
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutLMiguel, VirginiaCorrea, Elisa María Eugeniade Tullio, LuisinaBarra, Jose LuisArgaraña, Carlos EnriqueVillarreal, Marcos ArielP. aeruginosaMutLprotein-protein interactionBioinformatichttps://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6Mismatch Repair System corrects mutations arising from DNA replication that escape from DNA polymerase proofreadingactivity. This system consists of three main proteins, MutS-L-H, responsible for lesion recognition and repair. MutL is amember of GHKL ATPase family and its ATPase cycle has been proposed to modulate MutL activity during the repairprocess. Pseudomonas aeruginosa MutL (PaMutL) contains an N-terminal (NTD) ATPase domain connected by a linker to a C-terminal (CTD) dimerization domain that possesses metal ion-dependent endonuclease activity. With the aim to identifycharacteristics that allow the PaMutL NTD allosteric control of CTD endonuclease activity, we used an in silico andexperimental approach to determine the interaction surfaces of P. aeruginosa NTD (PaNTD), and compared it with the wellcharacterized Escherichia coli MutL NTD (EcNTD). Molecular dynamics simulations of PaNTD and EcNTD bound to or free ofadenosine nucleotides showed that a significant difference exists between the behavior of the EcNTD and PaNTDdimerization interface, particularly in the ATP lid. Structure based simulations of MutL homologues with endonucleaseactivity were performed that allowed an insight of the dimerization interface behavior in this family of proteins. Ourexperimental results show that, unlike EcNTD, PaNTD is dimeric in presence of ADP. Simulations in mixed solvent allowed usto identify the PaNTD putative DNA binding patch and a putative interaction patch located opposite to the dimerizationface. Structure based simulations of PaNTD dimer in presence of ADP or ATP suggest that nucleotide binding coulddifferentially modulate PaNTD protein-protein interactions. Far western assays performed in presence of ADP or ATP are inagreement with our in silico analysis.Fil: Miguel, Virginia. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p);Fil: Correa, Elisa María Eugenia. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p); ArgentinaFil: de Tullio, Luisina. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p); ArgentinaFil: Barra, Jose Luis. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p); ArgentinaFil: Argaraña, Carlos Enrique. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p);Fil: Villarreal, Marcos Ariel. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Instituto de Investigaciones En Fisico- Quimica de Cordoba; ArgentinaPublic Library Science2013-07-26info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/549Miguel, Virginia; Correa, Elisa María Eugenia; de Tullio, Luisina; Barra, Jose Luis; Argaraña, Carlos Enrique; Villarreal, Marcos Ariel; Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL; Public Library Science; Plos One; 8; 7; 26-7-2013; 69907-69907;1932-6203enginfo:eu-repo/semantics/altIdentifier/url/http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0069907info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:02:11Zoai:ri.conicet.gov.ar:11336/549instacron: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 11:02:12.075CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL
title Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL
spellingShingle Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL
Miguel, Virginia
P. aeruginosa
MutL
protein-protein interaction
Bioinformatic
title_short Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL
title_full Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL
title_fullStr Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL
title_full_unstemmed Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL
title_sort Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL
dc.creator.none.fl_str_mv Miguel, Virginia
Correa, Elisa María Eugenia
de Tullio, Luisina
Barra, Jose Luis
Argaraña, Carlos Enrique
Villarreal, Marcos Ariel
author Miguel, Virginia
author_facet Miguel, Virginia
Correa, Elisa María Eugenia
de Tullio, Luisina
Barra, Jose Luis
Argaraña, Carlos Enrique
Villarreal, Marcos Ariel
author_role author
author2 Correa, Elisa María Eugenia
de Tullio, Luisina
Barra, Jose Luis
Argaraña, Carlos Enrique
Villarreal, Marcos Ariel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv P. aeruginosa
MutL
protein-protein interaction
Bioinformatic
topic P. aeruginosa
MutL
protein-protein interaction
Bioinformatic
purl_subject.fl_str_mv https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
dc.description.none.fl_txt_mv Mismatch Repair System corrects mutations arising from DNA replication that escape from DNA polymerase proofreadingactivity. This system consists of three main proteins, MutS-L-H, responsible for lesion recognition and repair. MutL is amember of GHKL ATPase family and its ATPase cycle has been proposed to modulate MutL activity during the repairprocess. Pseudomonas aeruginosa MutL (PaMutL) contains an N-terminal (NTD) ATPase domain connected by a linker to a C-terminal (CTD) dimerization domain that possesses metal ion-dependent endonuclease activity. With the aim to identifycharacteristics that allow the PaMutL NTD allosteric control of CTD endonuclease activity, we used an in silico andexperimental approach to determine the interaction surfaces of P. aeruginosa NTD (PaNTD), and compared it with the wellcharacterized Escherichia coli MutL NTD (EcNTD). Molecular dynamics simulations of PaNTD and EcNTD bound to or free ofadenosine nucleotides showed that a significant difference exists between the behavior of the EcNTD and PaNTDdimerization interface, particularly in the ATP lid. Structure based simulations of MutL homologues with endonucleaseactivity were performed that allowed an insight of the dimerization interface behavior in this family of proteins. Ourexperimental results show that, unlike EcNTD, PaNTD is dimeric in presence of ADP. Simulations in mixed solvent allowed usto identify the PaNTD putative DNA binding patch and a putative interaction patch located opposite to the dimerizationface. Structure based simulations of PaNTD dimer in presence of ADP or ATP suggest that nucleotide binding coulddifferentially modulate PaNTD protein-protein interactions. Far western assays performed in presence of ADP or ATP are inagreement with our in silico analysis.
Fil: Miguel, Virginia. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p);
Fil: Correa, Elisa María Eugenia. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p); Argentina
Fil: de Tullio, Luisina. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p); Argentina
Fil: Barra, Jose Luis. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p); Argentina
Fil: Argaraña, Carlos Enrique. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p);
Fil: Villarreal, Marcos Ariel. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Instituto de Investigaciones En Fisico- Quimica de Cordoba; Argentina
description Mismatch Repair System corrects mutations arising from DNA replication that escape from DNA polymerase proofreadingactivity. This system consists of three main proteins, MutS-L-H, responsible for lesion recognition and repair. MutL is amember of GHKL ATPase family and its ATPase cycle has been proposed to modulate MutL activity during the repairprocess. Pseudomonas aeruginosa MutL (PaMutL) contains an N-terminal (NTD) ATPase domain connected by a linker to a C-terminal (CTD) dimerization domain that possesses metal ion-dependent endonuclease activity. With the aim to identifycharacteristics that allow the PaMutL NTD allosteric control of CTD endonuclease activity, we used an in silico andexperimental approach to determine the interaction surfaces of P. aeruginosa NTD (PaNTD), and compared it with the wellcharacterized Escherichia coli MutL NTD (EcNTD). Molecular dynamics simulations of PaNTD and EcNTD bound to or free ofadenosine nucleotides showed that a significant difference exists between the behavior of the EcNTD and PaNTDdimerization interface, particularly in the ATP lid. Structure based simulations of MutL homologues with endonucleaseactivity were performed that allowed an insight of the dimerization interface behavior in this family of proteins. Ourexperimental results show that, unlike EcNTD, PaNTD is dimeric in presence of ADP. Simulations in mixed solvent allowed usto identify the PaNTD putative DNA binding patch and a putative interaction patch located opposite to the dimerizationface. Structure based simulations of PaNTD dimer in presence of ADP or ATP suggest that nucleotide binding coulddifferentially modulate PaNTD protein-protein interactions. Far western assays performed in presence of ADP or ATP are inagreement with our in silico analysis.
publishDate 2013
dc.date.none.fl_str_mv 2013-07-26
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/11336/549
Miguel, Virginia; Correa, Elisa María Eugenia; de Tullio, Luisina; Barra, Jose Luis; Argaraña, Carlos Enrique; Villarreal, Marcos Ariel; Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL; Public Library Science; Plos One; 8; 7; 26-7-2013; 69907-69907;
1932-6203
url http://hdl.handle.net/11336/549
identifier_str_mv Miguel, Virginia; Correa, Elisa María Eugenia; de Tullio, Luisina; Barra, Jose Luis; Argaraña, Carlos Enrique; Villarreal, Marcos Ariel; Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL; Public Library Science; Plos One; 8; 7; 26-7-2013; 69907-69907;
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0069907
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
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 12.982451

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