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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Detalles Bibliográficos
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
Descripción
Sumario: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.

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