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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...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
2009
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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. |
format | Text |
id | pubmed-2651959 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
record_format | MEDLINE/PubMed |
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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