Molecular basis of thermal stability in truncated (2/2) hemoglobins

Autores
Bustamante, Juan Pablo; Bonamore, Alessandra; Nadra, Alejandro Daniel; Sciamanna, Natascia; Boffi, Alberto; Estrin, Dario Ariel; Boechi, Leonardo
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Understanding the molecular mechanism through which proteins are functional at extreme high and low temperatures is one of the key issues in structural biology. To investigate this phenomenon, we have focused on two instructive truncated hemoglobins from Thermobifida fusca (Tf-trHbO) and Mycobacterium tuberculosis (Mt-trHbO); although the two proteins are structurally nearly identical, only the former is stable at high temperatures. Methods: We used molecular dynamics simulations at different temperatures as well as thermal melting profile measurements of both wild type proteins and two mutants designed to interchange the amino acid residue, either Pro or Gly, at E3 position. Results: The results show that the presence of a Pro at the E3 position is able to increase (by 8°) or decrease (by 4°) the melting temperature of Mt-trHbO and Tf-trHbO, respectively. We observed that the ProE3 alters the structure of the CD loop, making it more flexible. Conclusions: This gain in flexibility allows the protein to concentrate its fluctuations in this single loop and avoid unfolding. The alternate conformations of the CD loop also favor the formation of more salt-bridge interactions, together augmenting the protein's thermostability. General significance: These results indicate a clear structural and dynamical role of a key residue for thermal stability in truncated hemoglobins.
Fil: Bustamante, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Bonamore, Alessandra. Instituto de Investigaciones Universitarias Roma la Sapienza; Italia
Fil: Nadra, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Sciamanna, Natascia. Instituto de Investigaciones Universitarias Roma la Sapienza; Italia
Fil: Boffi, Alberto. Instituto de Investigaciones Universitarias Roma la Sapienza; Italia
Fil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Boechi, Leonardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Molecular Basis
Hemoglobins
Truncated
Thermal Stability
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:11336/30400
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/30400
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular basis of thermal stability in truncated (2/2) hemoglobinsBustamante, Juan PabloBonamore, AlessandraNadra, Alejandro DanielSciamanna, NatasciaBoffi, AlbertoEstrin, Dario ArielBoechi, LeonardoMolecular BasisHemoglobinsTruncatedThermal Stabilityhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Background: Understanding the molecular mechanism through which proteins are functional at extreme high and low temperatures is one of the key issues in structural biology. To investigate this phenomenon, we have focused on two instructive truncated hemoglobins from Thermobifida fusca (Tf-trHbO) and Mycobacterium tuberculosis (Mt-trHbO); although the two proteins are structurally nearly identical, only the former is stable at high temperatures. Methods: We used molecular dynamics simulations at different temperatures as well as thermal melting profile measurements of both wild type proteins and two mutants designed to interchange the amino acid residue, either Pro or Gly, at E3 position. Results: The results show that the presence of a Pro at the E3 position is able to increase (by 8°) or decrease (by 4°) the melting temperature of Mt-trHbO and Tf-trHbO, respectively. We observed that the ProE3 alters the structure of the CD loop, making it more flexible. Conclusions: This gain in flexibility allows the protein to concentrate its fluctuations in this single loop and avoid unfolding. The alternate conformations of the CD loop also favor the formation of more salt-bridge interactions, together augmenting the protein's thermostability. General significance: These results indicate a clear structural and dynamical role of a key residue for thermal stability in truncated hemoglobins.Fil: Bustamante, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Bonamore, Alessandra. Instituto de Investigaciones Universitarias Roma la Sapienza; ItaliaFil: Nadra, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sciamanna, Natascia. Instituto de Investigaciones Universitarias Roma la Sapienza; ItaliaFil: Boffi, Alberto. Instituto de Investigaciones Universitarias Roma la Sapienza; ItaliaFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Boechi, Leonardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Science2014-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/30400Bustamante, Juan Pablo; Bonamore, Alessandra; Nadra, Alejandro Daniel; Sciamanna, Natascia; Boffi, Alberto; et al.; Molecular basis of thermal stability in truncated (2/2) hemoglobins; Elsevier Science; Biochimica et Biophysica Acta- General Subjects; 1840; 7; 4-2014; 2281-22880304-4165CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbagen.2014.03.018info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0304416514001226info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:48:17Zoai:ri.conicet.gov.ar:11336/30400instacron: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 11:48:18.014CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular basis of thermal stability in truncated (2/2) hemoglobins
title Molecular basis of thermal stability in truncated (2/2) hemoglobins
spellingShingle Molecular basis of thermal stability in truncated (2/2) hemoglobins
Bustamante, Juan Pablo
Molecular Basis
Hemoglobins
Truncated
Thermal Stability
title_short Molecular basis of thermal stability in truncated (2/2) hemoglobins
title_full Molecular basis of thermal stability in truncated (2/2) hemoglobins
title_fullStr Molecular basis of thermal stability in truncated (2/2) hemoglobins
title_full_unstemmed Molecular basis of thermal stability in truncated (2/2) hemoglobins
title_sort Molecular basis of thermal stability in truncated (2/2) hemoglobins
dc.creator.none.fl_str_mv Bustamante, Juan Pablo
Bonamore, Alessandra
Nadra, Alejandro Daniel
Sciamanna, Natascia
Boffi, Alberto
Estrin, Dario Ariel
Boechi, Leonardo
author Bustamante, Juan Pablo
author_facet Bustamante, Juan Pablo
Bonamore, Alessandra
Nadra, Alejandro Daniel
Sciamanna, Natascia
Boffi, Alberto
Estrin, Dario Ariel
Boechi, Leonardo
author_role author
author2 Bonamore, Alessandra
Nadra, Alejandro Daniel
Sciamanna, Natascia
Boffi, Alberto
Estrin, Dario Ariel
Boechi, Leonardo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Molecular Basis
Hemoglobins
Truncated
Thermal Stability
topic Molecular Basis
Hemoglobins
Truncated
Thermal Stability
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: Understanding the molecular mechanism through which proteins are functional at extreme high and low temperatures is one of the key issues in structural biology. To investigate this phenomenon, we have focused on two instructive truncated hemoglobins from Thermobifida fusca (Tf-trHbO) and Mycobacterium tuberculosis (Mt-trHbO); although the two proteins are structurally nearly identical, only the former is stable at high temperatures. Methods: We used molecular dynamics simulations at different temperatures as well as thermal melting profile measurements of both wild type proteins and two mutants designed to interchange the amino acid residue, either Pro or Gly, at E3 position. Results: The results show that the presence of a Pro at the E3 position is able to increase (by 8°) or decrease (by 4°) the melting temperature of Mt-trHbO and Tf-trHbO, respectively. We observed that the ProE3 alters the structure of the CD loop, making it more flexible. Conclusions: This gain in flexibility allows the protein to concentrate its fluctuations in this single loop and avoid unfolding. The alternate conformations of the CD loop also favor the formation of more salt-bridge interactions, together augmenting the protein's thermostability. General significance: These results indicate a clear structural and dynamical role of a key residue for thermal stability in truncated hemoglobins.
Fil: Bustamante, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Bonamore, Alessandra. Instituto de Investigaciones Universitarias Roma la Sapienza; Italia
Fil: Nadra, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Sciamanna, Natascia. Instituto de Investigaciones Universitarias Roma la Sapienza; Italia
Fil: Boffi, Alberto. Instituto de Investigaciones Universitarias Roma la Sapienza; Italia
Fil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Boechi, Leonardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Background: Understanding the molecular mechanism through which proteins are functional at extreme high and low temperatures is one of the key issues in structural biology. To investigate this phenomenon, we have focused on two instructive truncated hemoglobins from Thermobifida fusca (Tf-trHbO) and Mycobacterium tuberculosis (Mt-trHbO); although the two proteins are structurally nearly identical, only the former is stable at high temperatures. Methods: We used molecular dynamics simulations at different temperatures as well as thermal melting profile measurements of both wild type proteins and two mutants designed to interchange the amino acid residue, either Pro or Gly, at E3 position. Results: The results show that the presence of a Pro at the E3 position is able to increase (by 8°) or decrease (by 4°) the melting temperature of Mt-trHbO and Tf-trHbO, respectively. We observed that the ProE3 alters the structure of the CD loop, making it more flexible. Conclusions: This gain in flexibility allows the protein to concentrate its fluctuations in this single loop and avoid unfolding. The alternate conformations of the CD loop also favor the formation of more salt-bridge interactions, together augmenting the protein's thermostability. General significance: These results indicate a clear structural and dynamical role of a key residue for thermal stability in truncated hemoglobins.
publishDate 2014
dc.date.none.fl_str_mv 2014-04
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/11336/30400
Bustamante, Juan Pablo; Bonamore, Alessandra; Nadra, Alejandro Daniel; Sciamanna, Natascia; Boffi, Alberto; et al.; Molecular basis of thermal stability in truncated (2/2) hemoglobins; Elsevier Science; Biochimica et Biophysica Acta- General Subjects; 1840; 7; 4-2014; 2281-2288
0304-4165
CONICET Digital
CONICET
url http://hdl.handle.net/11336/30400
identifier_str_mv Bustamante, Juan Pablo; Bonamore, Alessandra; Nadra, Alejandro Daniel; Sciamanna, Natascia; Boffi, Alberto; et al.; Molecular basis of thermal stability in truncated (2/2) hemoglobins; Elsevier Science; Biochimica et Biophysica Acta- General Subjects; 1840; 7; 4-2014; 2281-2288
0304-4165
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbagen.2014.03.018
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0304416514001226
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 Elsevier Science
publisher.none.fl_str_mv Elsevier 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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