A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies

Autores
Romasanta, Pablo Nicolas; Curto, Lucrecia María; Urtasun, Nicolás; Sarratea, Maria Belén; Chiappini, Santiago Andrés; Miranda, Maria Victoria; Delfino, Jose Maria; Mariuzza, Roy A.; Fernández, Marisa Mariel; Malchiodi, Emilio Luis
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Natural killer (NK) cells discriminate between healthy and virally infected or transformed cells using diverse surface receptors that are both activating and inhibitory. Among them, the homodimeric Ly49 NK receptors, which can adopt two distinct conformations (backfolded and extended), are of particular importance for detecting cells infected with mouse cytomegalovirus (CMV) via recognition of the viral immunoevasin m157. The interaction of m157 with activating (Ly49H) and inhibitory (Ly49I) receptors governs the spread of mouseCMV.Wecarried out kinetic and thermodynamic experiments to elucidate the Ly49/m157 binding mechanism. Combining surface plasmon resonance, fluorescence anisotropy, and circular dichroism (CD), we determined that the best model to describe both the Ly49H/m157 and Ly49I/m157 interactions is a conformational selection mechanism where only the extended conformation of Ly49 (Ly49*) is able to bind the first m157 ligand followed by binding of the Ly49*/m157 complex to the second m157. The interaction is characterized by strong positive cooperativity such that the second m157 binds the Ly49 homodimer with a 1000-fold higher sequential constant than the first m157 (108 versus 105 M-1). Using far-UV CD, we obtained evidence for a conformational change in Ly49 upon binding m157 that could explain the positive cooperativity. The rate-limiting step of the overall mechanism is a conformational transition in Ly49 from its backfolded to extended form. The global thermodynamic parameters from the initial state (backfolded Ly49 and m157) to the final state (Ly49*/(m157)2) are characterized by an unfavorable enthalpy that is compensated by a favorable entropy, making the interaction spontaneous.
Fil: Romasanta, Pablo Nicolas. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Fil: Curto, Lucrecia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Urtasun, Nicolás. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Sarratea, Maria Belén. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Fil: Chiappini, Santiago Andrés. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Fil: Miranda, Maria Victoria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Delfino, Jose Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Mariuzza, Roy A.. University Of Maryland. Biotechnology Institute; Estados Unidos
Fil: Fernández, Marisa Mariel. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Fil: Malchiodi, Emilio Luis. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Materia
LY49
INNATE IMMUNITY
SPR
NATURAL KILLER CELL
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:11336/8045
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studiesRomasanta, Pablo NicolasCurto, Lucrecia MaríaUrtasun, NicolásSarratea, Maria BelénChiappini, Santiago AndrésMiranda, Maria VictoriaDelfino, Jose MariaMariuzza, Roy A.Fernández, Marisa MarielMalchiodi, Emilio LuisLY49INNATE IMMUNITYSPRNATURAL KILLER CELLhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Natural killer (NK) cells discriminate between healthy and virally infected or transformed cells using diverse surface receptors that are both activating and inhibitory. Among them, the homodimeric Ly49 NK receptors, which can adopt two distinct conformations (backfolded and extended), are of particular importance for detecting cells infected with mouse cytomegalovirus (CMV) via recognition of the viral immunoevasin m157. The interaction of m157 with activating (Ly49H) and inhibitory (Ly49I) receptors governs the spread of mouseCMV.Wecarried out kinetic and thermodynamic experiments to elucidate the Ly49/m157 binding mechanism. Combining surface plasmon resonance, fluorescence anisotropy, and circular dichroism (CD), we determined that the best model to describe both the Ly49H/m157 and Ly49I/m157 interactions is a conformational selection mechanism where only the extended conformation of Ly49 (Ly49*) is able to bind the first m157 ligand followed by binding of the Ly49*/m157 complex to the second m157. The interaction is characterized by strong positive cooperativity such that the second m157 binds the Ly49 homodimer with a 1000-fold higher sequential constant than the first m157 (108 versus 105 M-1). Using far-UV CD, we obtained evidence for a conformational change in Ly49 upon binding m157 that could explain the positive cooperativity. The rate-limiting step of the overall mechanism is a conformational transition in Ly49 from its backfolded to extended form. The global thermodynamic parameters from the initial state (backfolded Ly49 and m157) to the final state (Ly49*/(m157)2) are characterized by an unfavorable enthalpy that is compensated by a favorable entropy, making the interaction spontaneous.Fil: Romasanta, Pablo Nicolas. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Curto, Lucrecia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Urtasun, Nicolás. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Sarratea, Maria Belén. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Chiappini, Santiago Andrés. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Miranda, Maria Victoria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Delfino, Jose Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Mariuzza, Roy A.. University Of Maryland. Biotechnology Institute; Estados UnidosFil: Fernández, Marisa Mariel. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Malchiodi, Emilio Luis. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaAmerican Society For Biochemistry And Molecular Biology2014-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8045Romasanta, Pablo Nicolas; Curto, Lucrecia María; Urtasun, Nicolás; Sarratea, Maria Belén; Chiappini, Santiago Andrés; et al.; A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 289; 2-2014; 5083-50960021-9258enginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/289/8/5083.longinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931067/info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M113.532929info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:08:27Zoai:ri.conicet.gov.ar:11336/8045instacron: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:34982025-09-10 13:08:27.453CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies
title A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies
spellingShingle A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies
Romasanta, Pablo Nicolas
LY49
INNATE IMMUNITY
SPR
NATURAL KILLER CELL
title_short A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies
title_full A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies
title_fullStr A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies
title_full_unstemmed A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies
title_sort A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies
dc.creator.none.fl_str_mv Romasanta, Pablo Nicolas
Curto, Lucrecia María
Urtasun, Nicolás
Sarratea, Maria Belén
Chiappini, Santiago Andrés
Miranda, Maria Victoria
Delfino, Jose Maria
Mariuzza, Roy A.
Fernández, Marisa Mariel
Malchiodi, Emilio Luis
author Romasanta, Pablo Nicolas
author_facet Romasanta, Pablo Nicolas
Curto, Lucrecia María
Urtasun, Nicolás
Sarratea, Maria Belén
Chiappini, Santiago Andrés
Miranda, Maria Victoria
Delfino, Jose Maria
Mariuzza, Roy A.
Fernández, Marisa Mariel
Malchiodi, Emilio Luis
author_role author
author2 Curto, Lucrecia María
Urtasun, Nicolás
Sarratea, Maria Belén
Chiappini, Santiago Andrés
Miranda, Maria Victoria
Delfino, Jose Maria
Mariuzza, Roy A.
Fernández, Marisa Mariel
Malchiodi, Emilio Luis
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv LY49
INNATE IMMUNITY
SPR
NATURAL KILLER CELL
topic LY49
INNATE IMMUNITY
SPR
NATURAL KILLER CELL
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Natural killer (NK) cells discriminate between healthy and virally infected or transformed cells using diverse surface receptors that are both activating and inhibitory. Among them, the homodimeric Ly49 NK receptors, which can adopt two distinct conformations (backfolded and extended), are of particular importance for detecting cells infected with mouse cytomegalovirus (CMV) via recognition of the viral immunoevasin m157. The interaction of m157 with activating (Ly49H) and inhibitory (Ly49I) receptors governs the spread of mouseCMV.Wecarried out kinetic and thermodynamic experiments to elucidate the Ly49/m157 binding mechanism. Combining surface plasmon resonance, fluorescence anisotropy, and circular dichroism (CD), we determined that the best model to describe both the Ly49H/m157 and Ly49I/m157 interactions is a conformational selection mechanism where only the extended conformation of Ly49 (Ly49*) is able to bind the first m157 ligand followed by binding of the Ly49*/m157 complex to the second m157. The interaction is characterized by strong positive cooperativity such that the second m157 binds the Ly49 homodimer with a 1000-fold higher sequential constant than the first m157 (108 versus 105 M-1). Using far-UV CD, we obtained evidence for a conformational change in Ly49 upon binding m157 that could explain the positive cooperativity. The rate-limiting step of the overall mechanism is a conformational transition in Ly49 from its backfolded to extended form. The global thermodynamic parameters from the initial state (backfolded Ly49 and m157) to the final state (Ly49*/(m157)2) are characterized by an unfavorable enthalpy that is compensated by a favorable entropy, making the interaction spontaneous.
Fil: Romasanta, Pablo Nicolas. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Fil: Curto, Lucrecia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Urtasun, Nicolás. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Sarratea, Maria Belén. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Fil: Chiappini, Santiago Andrés. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Fil: Miranda, Maria Victoria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Delfino, Jose Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Mariuzza, Roy A.. University Of Maryland. Biotechnology Institute; Estados Unidos
Fil: Fernández, Marisa Mariel. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Fil: Malchiodi, Emilio Luis. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
description Natural killer (NK) cells discriminate between healthy and virally infected or transformed cells using diverse surface receptors that are both activating and inhibitory. Among them, the homodimeric Ly49 NK receptors, which can adopt two distinct conformations (backfolded and extended), are of particular importance for detecting cells infected with mouse cytomegalovirus (CMV) via recognition of the viral immunoevasin m157. The interaction of m157 with activating (Ly49H) and inhibitory (Ly49I) receptors governs the spread of mouseCMV.Wecarried out kinetic and thermodynamic experiments to elucidate the Ly49/m157 binding mechanism. Combining surface plasmon resonance, fluorescence anisotropy, and circular dichroism (CD), we determined that the best model to describe both the Ly49H/m157 and Ly49I/m157 interactions is a conformational selection mechanism where only the extended conformation of Ly49 (Ly49*) is able to bind the first m157 ligand followed by binding of the Ly49*/m157 complex to the second m157. The interaction is characterized by strong positive cooperativity such that the second m157 binds the Ly49 homodimer with a 1000-fold higher sequential constant than the first m157 (108 versus 105 M-1). Using far-UV CD, we obtained evidence for a conformational change in Ly49 upon binding m157 that could explain the positive cooperativity. The rate-limiting step of the overall mechanism is a conformational transition in Ly49 from its backfolded to extended form. The global thermodynamic parameters from the initial state (backfolded Ly49 and m157) to the final state (Ly49*/(m157)2) are characterized by an unfavorable enthalpy that is compensated by a favorable entropy, making the interaction spontaneous.
publishDate 2014
dc.date.none.fl_str_mv 2014-02
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/11336/8045
Romasanta, Pablo Nicolas; Curto, Lucrecia María; Urtasun, Nicolás; Sarratea, Maria Belén; Chiappini, Santiago Andrés; et al.; A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 289; 2-2014; 5083-5096
0021-9258
url http://hdl.handle.net/11336/8045
identifier_str_mv Romasanta, Pablo Nicolas; Curto, Lucrecia María; Urtasun, Nicolás; Sarratea, Maria Belén; Chiappini, Santiago Andrés; et al.; A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 289; 2-2014; 5083-5096
0021-9258
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/289/8/5083.long
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931067/
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M113.532929
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/
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dc.publisher.none.fl_str_mv American Society For Biochemistry And Molecular Biology
publisher.none.fl_str_mv American Society For Biochemistry And Molecular Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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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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