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

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...

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Autores principales:	Bustamante, Juan Pablo, Nadra, Alejandro Daniel, Estrin, Dario Ariel, Boechi, Leonardo
Publicado:	2014
Materias:	Folding Molecular dynamics Mycobacterium tuberculosis Thermobifida fusca Thermostability Truncated hemoglobin glycine proline truncated hemoglobin amino acid substitution article computer simulation controlled study hemoglobin analysis melting point molecular dynamics molecular interaction nonhuman priority journal protein conformation protein expression protein stability protein structure protein unfolding thermostability wild type Actinomycetales Hot Temperature Humans Models, Molecular Molecular Dynamics Simulation Protein Stability Truncated Hemoglobins
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03044165_v1840_n7_p2281_Bustamante http://hdl.handle.net/20.500.12110/paper_03044165_v1840_n7_p2281_Bustamante
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_03044165_v1840_n7_p2281_Bustamante
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spelling	paper:paper_03044165_v1840_n7_p2281_Bustamante2023-06-08T15:29:53Z Molecular basis of thermal stability in truncated (2/2) hemoglobins Bustamante, Juan Pablo Nadra, Alejandro Daniel Estrin, Dario Ariel Boechi, Leonardo Folding Molecular dynamics Mycobacterium tuberculosis Thermobifida fusca Thermostability Truncated hemoglobin glycine proline truncated hemoglobin amino acid substitution article computer simulation controlled study hemoglobin analysis melting point molecular dynamics molecular interaction Mycobacterium tuberculosis nonhuman priority journal protein conformation protein expression protein stability protein structure protein unfolding Thermobifida fusca thermostability wild type Folding Molecular dynamics Mycobacterium tuberculosis Thermobifida fusca Thermostability Truncated hemoglobin Actinomycetales Hot Temperature Humans Models, Molecular Molecular Dynamics Simulation Mycobacterium tuberculosis Protein Stability Truncated Hemoglobins 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. © 2014 Elsevier B.V. Fil:Bustamante, J.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Nadra, A.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Boechi, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03044165_v1840_n7_p2281_Bustamante http://hdl.handle.net/20.500.12110/paper_03044165_v1840_n7_p2281_Bustamante
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Folding Molecular dynamics Mycobacterium tuberculosis Thermobifida fusca Thermostability Truncated hemoglobin glycine proline truncated hemoglobin amino acid substitution article computer simulation controlled study hemoglobin analysis melting point molecular dynamics molecular interaction Mycobacterium tuberculosis nonhuman priority journal protein conformation protein expression protein stability protein structure protein unfolding Thermobifida fusca thermostability wild type Folding Molecular dynamics Mycobacterium tuberculosis Thermobifida fusca Thermostability Truncated hemoglobin Actinomycetales Hot Temperature Humans Models, Molecular Molecular Dynamics Simulation Mycobacterium tuberculosis Protein Stability Truncated Hemoglobins
spellingShingle	Folding Molecular dynamics Mycobacterium tuberculosis Thermobifida fusca Thermostability Truncated hemoglobin glycine proline truncated hemoglobin amino acid substitution article computer simulation controlled study hemoglobin analysis melting point molecular dynamics molecular interaction Mycobacterium tuberculosis nonhuman priority journal protein conformation protein expression protein stability protein structure protein unfolding Thermobifida fusca thermostability wild type Folding Molecular dynamics Mycobacterium tuberculosis Thermobifida fusca Thermostability Truncated hemoglobin Actinomycetales Hot Temperature Humans Models, Molecular Molecular Dynamics Simulation Mycobacterium tuberculosis Protein Stability Truncated Hemoglobins Bustamante, Juan Pablo Nadra, Alejandro Daniel Estrin, Dario Ariel Boechi, Leonardo Molecular basis of thermal stability in truncated (2/2) hemoglobins
topic_facet	Folding Molecular dynamics Mycobacterium tuberculosis Thermobifida fusca Thermostability Truncated hemoglobin glycine proline truncated hemoglobin amino acid substitution article computer simulation controlled study hemoglobin analysis melting point molecular dynamics molecular interaction Mycobacterium tuberculosis nonhuman priority journal protein conformation protein expression protein stability protein structure protein unfolding Thermobifida fusca thermostability wild type Folding Molecular dynamics Mycobacterium tuberculosis Thermobifida fusca Thermostability Truncated hemoglobin Actinomycetales Hot Temperature Humans Models, Molecular Molecular Dynamics Simulation Mycobacterium tuberculosis Protein Stability Truncated Hemoglobins
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. © 2014 Elsevier B.V.
author	Bustamante, Juan Pablo Nadra, Alejandro Daniel Estrin, Dario Ariel Boechi, Leonardo
author_facet	Bustamante, Juan Pablo Nadra, Alejandro Daniel Estrin, Dario Ariel Boechi, Leonardo
author_sort	Bustamante, Juan Pablo
title	Molecular basis of thermal stability in truncated (2/2) hemoglobins
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
publishDate	2014
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03044165_v1840_n7_p2281_Bustamante http://hdl.handle.net/20.500.12110/paper_03044165_v1840_n7_p2281_Bustamante
work_keys_str_mv	AT bustamantejuanpablo molecularbasisofthermalstabilityintruncated22hemoglobins AT nadraalejandrodaniel molecularbasisofthermalstabilityintruncated22hemoglobins AT estrindarioariel molecularbasisofthermalstabilityintruncated22hemoglobins AT boechileonardo molecularbasisofthermalstabilityintruncated22hemoglobins
_version_	1768544595516325888

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

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