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The Mechanism of Folding of Im7 Reveals Competition between Functional and Kinetic Evolutionary Constraints

Many proteins reach their native state through pathways involving the presence of folding intermediates. It is not clear whether this type of folding landscape results from insufficient evolutionary pressure to optimize folding efficiency, or arises from a conflict between functional and folding con...

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Detalles Bibliográficos
Autores principales: Friel, Claire T., Smith, D. Alastair, Vendruscolo, Michele, Gsponer, Joerg, Radford, Sheena E.
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651959/
https://www.ncbi.nlm.nih.gov/pubmed/19252485
http://dx.doi.org/10.1038/nsmb.1562
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author Friel, Claire T.
Smith, D. Alastair
Vendruscolo, Michele
Gsponer, Joerg
Radford, Sheena E.
author_facet Friel, Claire T.
Smith, D. Alastair
Vendruscolo, Michele
Gsponer, Joerg
Radford, Sheena E.
author_sort Friel, Claire T.
collection PubMed
description Many proteins reach their native state through pathways involving the presence of folding intermediates. It is not clear whether this type of folding landscape results from insufficient evolutionary pressure to optimize folding efficiency, or arises from a conflict between functional and folding constraints. Here, using protein-engineering, ultra-rapid mixing and stopped-flow experiments combined with restrained molecular dynamics simulations, we characterize the transition state for the formation of the intermediate populated during the folding of the bacterial immunity protein, Im7, and the subsequent molecular steps leading to the native state. The results provide a comprehensive view of the folding process of this small protein. An analysis of the contributions of native and non-native interactions at different stages of folding reveals how the complexity of the folding landscape arises from concomitant evolutionary pressures for function and folding efficiency.
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spelling pubmed-26519592009-09-01 The Mechanism of Folding of Im7 Reveals Competition between Functional and Kinetic Evolutionary Constraints Friel, Claire T. Smith, D. Alastair Vendruscolo, Michele Gsponer, Joerg Radford, Sheena E. Nat Struct Mol Biol Article Many proteins reach their native state through pathways involving the presence of folding intermediates. It is not clear whether this type of folding landscape results from insufficient evolutionary pressure to optimize folding efficiency, or arises from a conflict between functional and folding constraints. Here, using protein-engineering, ultra-rapid mixing and stopped-flow experiments combined with restrained molecular dynamics simulations, we characterize the transition state for the formation of the intermediate populated during the folding of the bacterial immunity protein, Im7, and the subsequent molecular steps leading to the native state. The results provide a comprehensive view of the folding process of this small protein. An analysis of the contributions of native and non-native interactions at different stages of folding reveals how the complexity of the folding landscape arises from concomitant evolutionary pressures for function and folding efficiency. 2009-03-01 2009-03 /pmc/articles/PMC2651959/ /pubmed/19252485 http://dx.doi.org/10.1038/nsmb.1562 Text en
spellingShingle Article
Friel, Claire T.
Smith, D. Alastair
Vendruscolo, Michele
Gsponer, Joerg
Radford, Sheena E.
The Mechanism of Folding of Im7 Reveals Competition between Functional and Kinetic Evolutionary Constraints
title The Mechanism of Folding of Im7 Reveals Competition between Functional and Kinetic Evolutionary Constraints
title_full The Mechanism of Folding of Im7 Reveals Competition between Functional and Kinetic Evolutionary Constraints
title_fullStr The Mechanism of Folding of Im7 Reveals Competition between Functional and Kinetic Evolutionary Constraints
title_full_unstemmed The Mechanism of Folding of Im7 Reveals Competition between Functional and Kinetic Evolutionary Constraints
title_short The Mechanism of Folding of Im7 Reveals Competition between Functional and Kinetic Evolutionary Constraints
title_sort mechanism of folding of im7 reveals competition between functional and kinetic evolutionary constraints
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651959/
https://www.ncbi.nlm.nih.gov/pubmed/19252485
http://dx.doi.org/10.1038/nsmb.1562
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